Medicament delivery device for administration of opioid antagonists including formulations for naloxone

ABSTRACT

Medicament delivery devices for administration of opioid antagonists are described herein. In some embodiments, an apparatus includes a housing, a medicament container disposed within the housing and an energy storage member disposed within the housing. The medicament container is filled with a naloxone composition that includes naloxone or salts thereof, a tonicity-adjusting agent, and a pH adjusting agent, whereby the osmolality of the naloxone composition ranges from about 250-350 mOsm and the pH ranges from about 3-5. The energy storage member is configured to produce a force to deliver the naloxone composition.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/694,725, filed Apr. 23, 2015, which is a continuation of U.S. patentapplication Ser. No. 14/153,575, filed Jan. 13, 2014, now U.S. Pat. No.9,022,022, which is a continuation of U.S. patent application Ser. No.13/036,720, filed Feb. 28, 2011, now U.S. Pat. No. 8,627,816, eachentitled “Medicament Delivery Device for Administration of OpioidAntagonists Including Formulations for Naloxone,” and each of which isincorporated herein by reference in its entirety.

BACKGROUND

The embodiments described herein relate generally to medical device andpharmaceutical compositions, and more particularly to a medicamentdelivery device for administration of opioid antagonists, includingformulations for naloxone.

Naloxone is a medicament that prevents and/or reverses the effects ofopioids. Known formulations of naloxone can be used, for example, totreat respiratory depression and other indications that result fromopioid toxicity. For example, known formulations for naloxone can beused to reverse and/or mitigate the effects of an overdose of a drugcontaining opioids, such as, for example, heroin. In such situations, itis desirable to deliver the naloxone formulation quickly and in a mannerthat will produce a rapid onset of action. Accordingly, knownformulations of naloxone are often delivered either intranasally or viainjection.

The delivery of naloxone intranasally or via injection, however, ofteninvolves completing a series of operations that, if not done properly,can limit the effectiveness of the naloxone formulation. For example,prior to delivering the naloxone, the user must first determine whetherthe patient's symptoms warrant the delivery of naloxone, and then couplea needle (or an atomizer) to a syringe containing the naloxoneformulation. After the device is prepared for delivery, the user thenselects the region of the body in which the naloxone is to be delivered,and manually produces a force to deliver the naloxone. In somesituations, such as, for example, when the patient is in an ambulance ora hospital setting, the user then inserts an intravenous catheter toadminister the naloxone. Additionally, after the delivery of thenaloxone formulation, the user must dispose of the device properly(e.g., to prevent needle sticks in instances where the naloxone isinjected) and seek further medical attention for the patient.Accordingly, known formulations of naloxone are often delivered by ahealthcare provider in a controlled environment (e.g. a hospital,physician's office, clinic or the like). Access to emergency medicalfacilities and/or trained health care providers, however, is not alwaysavailable when an individual is suffering from an overdose. Moreover,because naloxone is often administered during an emergency situation,even experienced and/or trained users may be subject to confusion and/orpanic, thereby compromising the delivery of the naloxone formulation.

Known devices for delivering naloxone also require that the usermanually generate the force and/or pressure required to convey thenaloxone from the device into the body. For example, to deliver naloxoneusing known syringes, the user manually depresses a plunger into thesyringe body. The force generated by manually depressing a plunger,however, can be sporadic, thus resulting in undesirable fluctuations inthe flow of the naloxone and/or incomplete delivery of the full dose.Such fluctuations and variability can be particularly undesirable whenthe naloxone is being atomized for intranasal delivery. Moreover, incertain situations, the user may be unable to generate sufficient forceto provide the desired flow rate and/or flow characteristics (e.g., foran atomizer) of the naloxone.

Additionally, because naloxone is often delivered by a healthcareprovider in a controlled environment, known formulations of naloxone aregenerally stored under controlled conditions, and for limited periods oftime. For example, known naloxone formulations are often formulated tobe stored between 20 and 25 degrees Celsius. Accordingly, known naloxoneformulations are not compatible for being carried by a patient or athird party (e.g., a relative of friend of the patient) for long periodsof time.

Thus, a need exists for improved methods and devices for deliveringopioid antagonists, such as, for example, devices that provide for thedelivery of naloxone by untrained users. Additionally, a need exists fornaloxone formulations that can be exposed to a wide range ofenvironmental conditions for long periods of time.

SUMMARY

Medicament delivery devices for administration of opioid antagonists andchemical compositions used within such devices are described herein. Insome embodiments, a naloxone composition can be formulated for use in adelivery device of the types shown and described herein. The naloxonecomposition includes an effective amount of naloxone i.e.,4.5-epoxy-3,14-dihydroxy-17-(2-propenyl) morphinan-6-one, or apharmaceutically acceptable salt and/or ester thereof. As used herein,an “effective amount” is an amount sufficient to provide a desiredtherapeutic effect. In some embodiments, the naloxone composition caninclude a pH adjusting agent, such as, for example, at least one ofhydrochloric acid, citric acid, acetic acid, phosphoric acid, orcombinations thereof. In some embodiments, the naloxone composition caninclude one or more tonicity-adjusting agents, such as, for example, atleast one of dextrose, glycerin, mannitol, potassium chloride, sodiumchloride, or combinations thereof. Because the naloxone composition maybe stored in the medicament container of a delivery device for extendedperiods of time under varying storage conditions, in some embodimentsthe naloxone composition can include stabilizers to prevent or inhibitdecomposition of the naloxone during storage.

In some embodiments, an apparatus includes a housing, a medicamentcontainer disposed within the housing and an energy storage memberdisposed within the housing. The medicament container is filled with analoxone composition that includes naloxone or salts thereof, atonicity-adjusting agent, and a pH adjusting agent, whereby theosmolality of the naloxone composition ranges from about 250-350 mOsmand the pH ranges from about 3-5. The energy storage member isconfigured to produce a force to deliver the naloxone composition.

In some embodiments, the medicament delivery device can further includean elastomeric member disposed within the medicament container that isconfigured to be compatible with the naloxone composition. Said anotherway, in some embodiments, an elastomeric member disposed within themedicament container can be formulated to prevent undesired leachingand/or reaction with the naloxone composition. In some embodiments, theelastomeric member is formulated to include a polymer and a curingagent. The polymer includes at least one of bromobutyl or chlorobutyl,and the curing agent includes at least one of sulfur or metal compounds,e.g., metal oxides such as zinc oxide or magnesium oxide, etc.

In some embodiments, the medicament delivery device can include anelectronic circuit system coupled to the housing. The electronic circuitsystem is configured to produce an output when the electronic circuitsystem is actuated. The output can be, for example, an audible or visualoutput related to the naloxone composition (e.g., an indication of theexpiration date, the symptoms requirement treatment with naloxone or thelike), the use of the medicament delivery device, and/orpost-administration procedures (e.g., a prompt to call 911, instructionsfor the disposal of the device or the like).

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of a medicament delivery deviceaccording to an embodiment.

FIG. 2 is a schematic illustration of a medicament delivery deviceaccording to an embodiment.

FIG. 3 is a schematic illustration of a medicament delivery deviceaccording to an embodiment.

FIGS. 4 and 5 are perspective views of a medical injector according toan embodiment, in a first configuration.

FIG. 6 is a front view of the medical injector illustrated in FIG. 4with the cover removed.

FIG. 7 is a back view of the medical injector illustrated in FIG. 4 withthe cover removed.

FIG. 8 is a front view of a portion of the medical injector illustratedin FIG. 4.

FIG. 9 is a perspective view of a portion of the medical injectorillustrated in FIG. 4.

FIG. 10 is a bottom perspective view of a housing of the medicalinjector illustrated in FIG. 4.

FIG. 11 is a top perspective view of a housing of the medical injectorillustrated in FIG. 4.

FIG. 12 is a perspective view of a proximal cap of the medical injectorillustrated in FIG. 4.

FIGS. 13 and 14 are a front views of a medicament delivery mechanism ofthe medical injector illustrated in FIG. 4.

FIG. 15 is a perspective view of a portion of the medical injectorillustrated in FIG. 4.

FIG. 16 is an exploded view of a medicament container of the medicalinjector illustrated in FIG. 4.

FIG. 17 is a front view of a portion of the medical injector illustratedin FIG. 4.

FIG. 18 is a back view of an electronic circuit system of the medicalinjector illustrated in FIG. 4.

FIG. 19 is a front view of a portion of the electronic circuit system ofthe medical injector illustrated in FIG. 18.

FIG. 20 is a side view of the electronic circuit system of the medicalinjector illustrated in FIG. 18.

FIG. 21 is a front view of an electronic circuit system housing of theelectronic circuit system illustrated in FIG. 18.

FIG. 22 is a perspective view of the electronic circuit system housingof the electronic circuit system illustrated in FIG. 21.

FIG. 23 is a perspective view of a battery clip of the electroniccircuit system illustrated in FIG. 18.

FIG. 24 is a perspective view of a portion of an electronic circuitsystem of the medical injector illustrated in FIG. 4, in a firstconfiguration.

FIG. 25 is a front view of the medical injector illustrated in FIG. 4 ina first configuration showing the electronic circuit system.

FIGS. 26-28 are front views of a portion of the electronic circuitsystem of the medical injector labeled as Region Z in FIG. 25 in a firstconfiguration, a second configuration, and a third configuration,respectively.

FIGS. 29 and 30 are perspective views of a cover of the medical injectorillustrated in FIG. 4.

FIG. 31 is a perspective view of a safety lock of the medical injectorillustrated in FIG. 4.

FIG. 32 is a front view of the safety lock of the medical injectorillustrated in FIG. 31.

FIG. 33 is a bottom view of the safety lock of the medical injectorillustrated in FIG. 31.

FIG. 34 is a perspective view of a needle sheath of the safety lock ofthe medical injector illustrated in FIG. 31.

FIG. 35 is a perspective view of a base of the medical injectorillustrated in FIG. 4.

FIG. 36 is a front view of the medical injector illustrated in FIG. 4.

FIG. 37 is a back view of the medical injector illustrated in FIG. 4 ina second configuration.

FIG. 38 is a back view of the medical injector illustrated in FIG. 4 ina third configuration.

FIG. 39 is a back view of the medical injector illustrated in FIG. 4 ina fourth configuration (i.e., the needle insertion configuration).

FIG. 40 is a front view of the medical injector illustrated in FIG. 4 inthe fourth configuration (i.e., the needle insertion configuration).

FIG. 41 is a front view of the medical injector illustrated in FIG. 4 ina fifth configuration (i.e., the injection configuration).

FIG. 42 is a front view of the medical injector illustrated in FIG. 4 ina sixth configuration (i.e., the retraction configuration).

FIG. 43 is a perspective view of a housing of a medical injectoraccording to an embodiment.

FIG. 44 is a perspective view of an electronic circuit system of amedical injector according to an embodiment.

FIG. 45 is a back view of a printed circuit board of the electroniccircuit system shown in FIG. 44.

FIG. 46 is a schematic illustration of the electronic circuit systemshown in FIG. 44.

FIG. 47 is a perspective cross-sectional view of the housing and theelectronic circuit system illustrated in FIG. 43 and FIG. 44respectively.

FIG. 48 is a cross-sectional perspective view of a portion of theelectronic circuit system illustrated in FIG. 36, taken along line X-Xin FIG. 47.

FIG. 49 is a schematic illustration of a medicament delivery deviceaccording to an embodiment.

FIG. 50 is a schematic illustration of a kit including a medicamentcontainer according to an embodiment.

DETAILED DESCRIPTION

Medicament delivery devices for administration of opioid antagonists andchemical compositions used within such devices are described herein. Insome embodiments, a naloxone composition can be formulated for use in adelivery device of the types shown and described herein. The naloxonecomposition includes an effective amount of naloxone i.e.,4,5-epoxy-3,14-dihydroxy-17-(2-propenyl) morphinan-6-one, or apharmaceutically acceptable salt and/or ester thereof. As used herein,an “effective amount” is an amount sufficient to provide a desiredtherapeutic effect. In some embodiments, the naloxone composition caninclude a pH adjusting agent, such as, for example, at least one ofhydrochloric acid, citric acid, acetic acid, phosphoric acid, orcombinations thereof. In some embodiments, the naloxone composition caninclude one or more tonicity-adjusting agents, such as, for example, atleast one of dextrose, glycerin, mannitol, potassium chloride, sodiumchloride, or combinations thereof. Because the naloxone composition maybe stored in the medicament container of a delivery device for extendedperiods of time under varying storage conditions, in some embodimentsthe naloxone composition can include stabilizers to prevent or inhibitdecomposition of the naloxone during storage.

In some embodiments, a medicament delivery device includes a housing, amedicament container disposed within the housing and an energy storagemember disposed within the housing. The medicament container is filledwith a naloxone composition that includes naloxone or salts thereof, atonicity-adjusting agent, and a pH adjusting agent, whereby theosmolality of the naloxone composition ranges from about 250-350 mOsmand the pH ranges from about 3-5. The energy storage member isconfigured to produce a force to deliver the naloxone composition.

In some embodiments, the medicament delivery device can further includean elastomeric member disposed within the medicament container that isconfigured to be compatible with the naloxone composition. Said anotherway, in some embodiments, an elastomeric member disposed within themedicament container can be formulated to prevent undesired leachingand/or reaction with the naloxone composition. In some embodiments, theelastomeric member is formulated to include a polymer and a curingagent. The polymer includes at least one of bromobutyl or chlorobutyl,and the curing agent includes at least one of sulfur, zinc or magnesium.

In some embodiments, the medicament delivery device can include anelectronic circuit system coupled to the housing. The electronic circuitsystem is configured to produce an output when the electronic circuitsystem is actuated. The output can be, for example, an audible or visualoutput related to the naloxone composition (e.g., an indication of theexpiration date, the symptoms requirement treatment with naloxone or thelike), the use of the medicament delivery device, and/orpost-administration procedures (e.g., a prompt to call 911, instructionsfor the disposal of the device or the like).

In some embodiments, a medicament delivery device includes a housing, amedicament container disposed within the housing, a delivery membercoupled to the medicament container, and an energy storage member. Themedicament container is filled with a naloxone composition. The energystorage member is disposed within the housing, and is configured toproduce a force to deliver the naloxone composition from the medicamentcontainer via the delivery member such that the delivery member atomizesthe naloxone composition.

In some embodiments, a kit includes a case and a medicament containermovably disposed within the case. The medicament container filled with analoxone composition. The medicament container includes a deliverymember coupled thereto. The delivery member can be, for example, aneedle, an atomizer or any other mechanism through which the naloxonecomposition can be conveyed from the medicament container into a body.

As used in this specification and the appended claims, the words“proximal” and “distal” refer to direction closer to and away from,respectively, an operator of the medical device. Thus, for example, theend of the medicament delivery device contacting the patient's bodywould be the distal end of the medicament delivery device, while the endopposite the distal end would be the proximal end of the medicamentdelivery device.

Throughout the present specification, the terms “about” and/or“approximately” may be used in conjunction with numerical values and/orranges. The term “about” is understood to mean those values near to arecited value. For example, “about 40 [units]” may mean within ±25% of40 (e.g., from 30 to 50), within ±20%, ±15%, ±10%, ±9%, ±8%, ±7%, ±7%,±5%, ±4%, ±3%, ±2%, ±1%, less than ±1%, or any other value or range ofvalues therein or therebelow. Furthermore, the phrases “less than about[a value]” or “greater than about [a value]” should be understood inview of the definition of the term “about” provided herein. The terms“about” and “approximately” may be used interchangeably.

Throughout the present specification, numerical ranges are provided forcertain quantities. It is to be understood that these ranges compriseall subranges therein. Thus, the range “from 50 to 80” includes allpossible ranges therein (e.g., 51-79, 52-78, 53-77, 54-76, 55-75, 70-70,etc.). Furthermore, all values within a given range may be an endpointfor the range encompassed thereby (e.g., the range 50-80 includes theranges with endpoints such as 55-80, 50-75, etc.).

Throughout the present specification, the words “a” or “an” areunderstood to mean “one or more” unless explicitly stated otherwise.Further, the words “a” or “an” and the phrase “one or more” may be usedinterchangeably.

Compositions

In one aspect, the present disclosure relates to compositions comprisingnaloxone or a pharmaceutically acceptable salt thereof suitable for usein the medicament delivery devices disclosed herein. Accordingly, thepresent naloxone compositions may be adapted for various administrationroutes, depending on the apparatus in which such composition(s) are tobe employed. For example, in some embodiments, the present compositionsmay be adapted for transmucosal administration as, e.g., a nasal spray,or alternatively as a sublingual or buccal spray. In other embodiments,the present naloxone compositions may be adapted for parenteraladministration as, e.g., an injectable solution.

The present compositions generally comprise an effective amount ofnaloxone, i.e., 4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)morphinan-6-one, or a pharmaceutically acceptable salt and/or esterthereof. As used herein, an “effective amount” is an amount sufficientto provide a desired therapeutic effect. For example, as describedherein, the present naloxone compositions may be useful in treatingrespiratory depression and/or other indications associated with opioidtoxicity. Accordingly, an effective amount of naloxone in the presentcompositions may be an amount sufficient to treat such respiratorydepression and/or other indications associated with opioid toxicity. Thepresent naloxone compositions typically have a concentration of4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)morphinan-6-one (or a saltand/or ester thereof) between about 0.01 mg/mL and about 10 mg/mL (e.g.,between about 0.05 mg/mL and about 2 mg/mL, or any other value or rangeof values therein, including about 0.1 mg/mL, about 0.2 mg/mL, about 0.3mg/mL, about 0.4 mg/mL, about 0.5 mg/mL, about 0.6 mg/mL, about 0.7mg/mL, about 0.8 mg/mL, about 0.9 mg/mL, about 1.0 mg/mL, about 1.1mg/mL, about 1.2 mg/mL, about 1.3 mg/mL, about 1.4 mg/mL, about 1.5mg/mL, about 1.6 mg/mL, about 1.7 mg/mL, about 1.8 mg/mL, or about 1.9mg/mL).

In some embodiments, the present naloxone compositions comprise a pHadjusting agent. In some embodiments, the pH adjusting agent includes atleast one of hydrochloric acid, citric acid, acetic acid, phosphoricacid, or combinations thereof. The pH adjusting agent may comprise anorganic and/or inorganic acid or salt thereof (e.g., alkali metal salts[Li, Na, K, etc.], alkaline earth metal [e.g., Ca, Mg, etc.] salts,ammonium salts, etc.). In other embodiments, the pH adjusting agentincludes mixtures of one or more acids and one or more salts thereof.e.g., citric acid and citrate salts, acetic acid and acetate salts,phosphoric acid and phosphate salts, etc. In certain embodiments, the pHadjusting agent is added in an amount sufficient to provide a pH of thepresent naloxone compositions of from about 3 to about 5 (for example apH of about 3.0, about 3.1, about 3.2, about 3.3, about 3.4, about 3.5,about 3.6, about 3.7, about 3.8, about 3.9, about 4.0, about 4.1, about4.2, about 4.3, about 4.4, about 4.5, about 4.6, about 4.7, about 4.8,about 4.9, or about 5.0). Accordingly, the present compositions maycomprise naloxone salts of the pH adjusting agent employed. For example,in one embodiment, the pH adjusting agent is dilute aqueous hydrochloricacid, and the naloxone salt is naloxone.HCl (e.g.,4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)-morphinan-6-one hydrochloride).

Solvents suitable for use in the present compositions are notparticularly limited, provided they are pharmaceutically acceptable.Accordingly, any pharmaceutically acceptable solvent in which thecomponents of the present compositions are soluble, and which does notadversely affect the stability of the present compositions and/or thenaloxone and/or naloxone salts contained therein may be employed. Forexample, in a typical composition, the solvent is sterile water (e.g.,USP grade water for injection [WFI]).

In some embodiments, the present compositions may also comprise one ormore tonicity-adjusting agents. For example, the tonicity-adjustingagent may include at least one of dextrose, glycerin, mannitol,potassium chloride, sodium chloride, or combinations thereof. Thetonicity-adjusting agent(s) may be present in an amount of from about0.1 mg/mL to about 50 mg/mL (e.g., including about 0.5 mg/mL, about 1.0mg/mL, about 2.0 mg/mL, about 3.0 mg/mL, about 4.0 mg/mL, about 5.0mg/mL, about 10 mg/mL, about 15 mg/mL, about 20 mg/mL, about 25 mg/mL,about 30 mg/mL, about 35 mg/mL, about 40 mg/mL, or about 45 mg/mL). Inone embodiment, the tonicity-adjusting agent is sodium chloride, and theconcentration thereof is between about 0.1 mg/mL and about 20 mg/mL.Generally, in naloxone compositions as described herein which areadapted for injection and/or intranasal delivery, tonicity-adjustingagents are added to provide a desired osmolality. In some embodiments,the osmolality of the naloxone compositions described herein is fromabout 250 to about 350 mOsm.

Because the naloxone compositions disclosed herein may be stored in themedicament container of the devices described herein for extendedperiods of time under varying storage conditions, in some embodimentsthe present compositions may further comprise stabilizers to prevent orinhibit decomposition of the naloxone during storage. Various types ofpharmaceutically acceptable stabilizers can be used, includingantioxidants (e.g. substituted phenols such as BHT, TBHQ, BHA, or propylgallate; ascorbates such as ascorboyl palmitate, sodium ascorbate,ascorbic acid), complexing agents (e.g., cyclodextrins); or chelatingagents such as EDTA (and its salts), D-gluconic acid 6-lactone, sodiumor potassium gluconate, sodium triphosphate, and sodiumhexametaphosphate.

EXAMPLES

The chemical stability of several exemplary naloxone hydrochloridecompositions were evaluated at various pH and temperature conditions.The formulation of six development lots was performed to evaluate pH andorder of addition parameters for naloxone hydrochloride. Assay testingwas performed on aliquots of bulk formulation solution sampled prior tothe filtration process to determine if the filtration processcontributed to any API losses.

Exemplary naloxone compositions were prepared according to theformulations set forth in Table 1, below:

TABLE 1 Exemplary Naloxone Formulations. API API Mix NaCl NaCl Volume ofFinal Initial Order of Added Time Added Mix Time Initial Adjusted FinalpH Adjuster Weight Lot WFI (g) Addition (mg) (seconds) (g) (seconds) pHpH pH (mL) (g) 1 400.01 A 554.73 110 4.5000 98 5.52 3.01 2.99 4.1 500.002 400.15 B 555.10 86 4.5269 69 5.41 6.51 6.51 0.5 502.14 3 400.13 A554.95 104 4.5033 58 5.39 4.47 4.47 0.2 502.17 4 400.00 B 554.53 824.4999 87 5.37 3.01 3.01 4.0 502.15 5 399.99 A 554.59 85 4.5513 74 5.406.49 6.49 0.2 502.16 6 400.02 B 554.81 68 4.5020 70 5.45 4.50 4.49 0.2502.19 Final Formulation Solution Density = 1.0043 g/mL (Determinedduring the formulation process for Lot 1) Order of Addition: A = Water,NaCl, naloxone hydrochloride, pH adjuster B = Water, naloxonehydrochloride, NaCl, pH adjuster

There were no noticeable differences between the formulations from lotto lot. The order of addition of the components had no observable impacton the dissolution times for either the API (Naloxone Hydrochloride) orthe NaCl. Initial solution pH values indicated no observable differencesbetween the solutions prior to final pH adjustment. The volumes requiredfor the final pH adjustment were also consistent, indicating nosignificant differences between the lots.

Solutions were filtered after formulation to determine if filtrationafter formulation impacts overall solution API concentration.Pre-filtration assay values were consistent with the post-filtration(initial) assay results for each lot, as shown in Table 2, below:

TABLE 2 Filtration of Naloxone Formulations. Pre-FiltrationPost-Filtration Naloxone Hydro- Naloxone Hydro- Lot chloride (mg/mL)chloride (mg/mL) 1 1.02 1.02 2 1.00 1.00 3 1.01 1.00 4 1.02 1.01 5 1.000.99 6 1.01 0.99

Because the naloxone compositions described herein may be stored in themedicament container of the devices described herein for extendedperiods of time under varying storage conditions, initial testing wasperformed to support a stability study for the development lots ofnaloxone hydrochloride. Initial appearance, pH and assay results areshown in Table 3, below:

TABLE 3 Initial Appearance, pH and Assay Results Osmolality Assay LotReplicate Appearance (mOsm) pH (mg/mL) 1 1 Clear, colorless solutionfree 295 3.09 1.02 of visible particulate matter 2 Clear, colorlesssolution free 295 3.09 1.02 of visible particulate matter Mean (n = 2)295 3.09 1.02 2 1 Clear, colorless solution free 294 6.54 1.00 ofvisible particulate matter 2 Clear, colorless solution free 295 6.551.00 of visible particulate matter Mean (n = 2) 295 6.55 1.00 3 1 Clear,colorless solution free 292 4.92 1.00 of visible particulate matter 2Clear, colorless solution free 289 4.96 1.00 of visible particulatematter Mean (n = 2) 291 4.94 1.00 4 1 Clear, colorless solution free 2943.13 1.01 of visible particulate matter 2 Clear, colorless solution free294 3.14 1.01 of visible particulate matter Mean (n = 2) 294 3.14 1.01 51 Clear, colorless solution free 295 6.57 0.99 of visible particulatematter 2 Clear, colorless solution free 295 6.57 0.99 of visibleparticulate matter Mean (n = 2) 295 6.57 0.99 6 1 Clear, colorlesssolution free 292 4.95 0.99 of visible particulate matter 2 Clear,colorless solution free 290 4.99 0.99 of visible particulate matter Mean(n = 2) 291 4.97 0.99

The pH analysis of Lots 3 and 7 exhibited increases of 0.4 and 0.5,respectively, in comparison to the pH values obtained during theformulation process. To verify the initial bulk pH, an aliquot of bulkformulation solution for Lot 7 was removed from storage at 5° C. andallowed to equilibrate to room temperature. The determined pH was 4.52,confirming the final pH obtained during the formulation process.Analysis of related substances was performed for each individual sample,as shown in Table 4, below:

TABLE 4 Initial Related Substance Screening Results Unknown Mean ofTotal (Identified % Related Total Related Related Lot Replicate by RRT)Substance Substances (%) Substances (%) 1 1 NR NR NR NR 2 NR NR NR 2 1NR NR NR NR 2 0.559 0.05 0.05 3 1 NR NR NR NR 2 NR NR NR 4 1 NR NR NR NR2 NR NR NR 5 1 0.160 0.11 0.17 0.09 0.559 0.06 2 NR NR NR 6 1 NR NR NRNR 2 NR NR NR NR = Not Reportable (<0.05% Impurity)

In Table 4, % Related Substance=(Related Substance Peak Area/TotalIntegrated Area)×100. Peaks greater than or equal to 0.05% werereported. Replicates that exhibited levels of related substances thatwere not reportable were treated as 0.00% for determination of meantotal related substances.

One month stability testing was conducted as previously described, withthe following additional analyses:

-   -   pH analysis for all lots at the 25° C./60% RH condition    -   pH analysis for lots 1 and 4 at the 40° C./75% RH condition    -   Assay and Related Substances analysis for lots 1 and 4 at the        25° C./60% RH and 40° C./75% RH conditions

TABLE 5 One Month Stability Results - 70° C./75% RH Assay (mg/ LotReplicate Appearance pH mL) 1 1 Clear, colorless solution free ofvisible 3.28 1.02 particulate matter 2 Clear, colorless solution free ofvisible 3.25 1.01 particulate matter Mean (n = 2) 3.27 1.02 2 1 Clear,colorless solution free of visible 6.05 0.94 particulate matter 2 Clear,colorless solution free of visible 6.05 0.94 particulate matter Mean (n= 2) 6.05 0.94 3 1 Clear, colorless solution free of visible 5.32 0.97particulate matter 2 Clear, colorless solution free of visible 5.44 0.97particulate matter Mean (n = 2) 5.38 0.97 4 1 Clear, colorless solutionfree of visible 3.28 1.01 particulate matter 2 Clear, colorless solutionfree of visible 3.28 0.99 particulate matter Mean (n = 2) 3.28 1.00 5 1Clear, colorless solution free of visible 6.06 0.94 particulate matter 2Clear, colorless solution free of visible 6.05 0.93 particulate matterMean (n = 2) 6.06 0.93 6 1 Clear, colorless solution free of visible5.41 0.95 particulate matter 2 Clear, colorless solution free of visible5.27 0.96 particulate matter Mean (n = 2) 5.34 0.95

TABLE 7a One Month Related Substances Results - 70° C./75% RH - Lots 1-3Unknown Mean of Total (Identified % Related Total Related Related LotReplicate by RRT) Substance Substances (%) Substances (%) 1 1 0.038 0.110.42 0.46 0.404 0.19 0.597 0.12 2 0.038 0.13 0.50 0.404 0.23 0.597 0.142 1 0.034 0.08 4.94 4.77 0.038 0.21 0.089 0.08 0.118 0.08 0.136 4.230.403 0.11 1.029 0.15 2 0.034 0.07 4.59 0.038 0.17 0.089 0.08 0.136 4.040.403 0.10 1.028 0.13 3 1 0.038 0.19 2.79 2.94 0.118 0.06 0.136 2.170.403 0.15 0.596 0.06 1.026 0.17 2 0.038 0.19 3.09 0.117 0.05 0.136 2.460.403 0.15 0.596 0.05 1.024 0.19

TABLE 7b One Month Related Substances Results - 70° C./75% RH - Lots 4-6Unknown Mean of Total (Identified % Related Total Related Related LotReplicate by RRT) Substance Substances (%) Substances (%) 4 1 0.038 0.110.44 0.79 0.403 0.20 0.596 0.13 2 0.039 0.22 1.13 0.116 0.09 0.135 0.090.403 0.46 0.596 0.28 5 1 0.039 0.18 4.60 4.80 0.089 0.07 0.115 0.050.133 4.20 0.403 0.10 2 0.039 0.18 5.00 0.089 0.09 0.132 4.64 0.402 0.086 1 0.038 0.17 2.85 2.76 0.132 2.55 0.403 0.13 2 0.038 0.17 2.66 0.1140.06 0.132 2.31 0.402 0.13

TABLE 7 One Month Stability Results - 40° C./75% RH Lot Replicate pHAssay (mg/mL) 1 1 3.14 1.01 2 3.13 1.01 Mean (n = 2) 3.14 1.01 4 1 3.161.01 2 3.16 1.00 Mean (n = 2) 3.16 1.00

TABLE 8 One Month Related Substances Results - 40° C./75% RH UnknownMean of Total (Identified % Related Total Related Related Lot Replicateby RRT) Substance Substances (%) Substances (%) 1 1 NR NR NR NR 2 NR NRNR 4 1 0.592 0.05 0.05 0.22 2 0.040 0.12 0.38 0.115 0.06 0.592 0.19

TABLE 9 One Month Stability Results - 25° C./60% RH Lot Replicate pHAssay (mg/mL) 1 1 3.11 1.01 2 3.16 1.01 Mean (n = 2) 3.14 1.01 2 1 6.33No analysis performed 2 6.41 Mean (n = 2) 6.37 3 1 5.20 No analysisperformed 2 5.21 Mean (n = 2) 5.21 4 1 3.19 1.01 2 3.17 1.01 Mean (n =2) 3.18 1.01 5 1 6.32 No analysis performed 2 6.40 Mean (n = 2) 6.36 6 15.23 No analysis performed 2 5.24 Mean (n = 2) 5.24

TABLE 10 One Month Related Substances Results - 25° C./60% RH TotalUnknown Related Mean of Total (Identified % Related Substances RelatedLot Replicate by RRT) Substances (%) Substances (%) 1 1 NR NR NR NR 2 NRNR NR 4 1 NR NR NR NR 2 NR NR NR

Three month stability testing was conducted as previously described,including the following measurements:

-   -   pH analysis for all lots at the 25° C./60% RH condition    -   pH analysis for lots 1 and 4 at the 40° C./75% RH condition    -   Assay and Related Substances analysis for lots 1 and 4 at the        25° C./60% RH and 40° C./75% RH conditions

TABLE 11 Three Month Stability Results - 70° C./75% RH Assay (mg/ LotReplicate Appearance pH mL) 1 1 Clear, colorless solution free ofvisible 3.70 1.00 particulate matter 2 Clear, colorless solution free ofvisible 3.70 1.00 particulate matter Mean (n = 2) 3.70 1.00 4 1 Clear,colorless solution free of visible 3.74 0.96 particulate matter 2 Clear,colorless solution free of visible 3.77 0.94 particulate matter Mean (n= 2) 3.76 0.95

TABLE 12a Three Month Related Substances Results - 70° C./75% RH - Lot 1Unknown Mean of Total (Identified % Related Total Related Related LotReplicate by RRT) Substance Substances (%) Substances (%) 1 1 0.039 0.361.70 1.74 0.096 0.14 0.136 0.05 0.165 0.34 0.364 0.50 0.384 0.06 0.5550.19 1.112 0.06 2 0.039 0.39 1.79 0.096 0.15 0.136 0.05 0.165 0.41 0.3640.47 0.384 0.06 0.555 0.18 1.112 0.07

TABLE 12b Three Month Related Substances Results - 70° C./75% RH - Lot 4Unknown Mean of Total (Identified % Related Total Related Related LotReplicate by RRT) Substance Substances (%) Substances (%) 4 1 0.039 0.783.44 4.34 0.095 0.38 0.112 0.06 0.135 0.13 0.155 0.06 0.164 0.66 0.3120.07 0.363 0.76 0.383 0.10 0.554 0.29 1.111 0.14 2 0.039 1.16 5.23 0.0960.58 0.112 0.11 0.135 0.21 0.155 0.07 0.164 0.96 0.312 0.11 0.363 1.190.383 0.14 0.553 0.46 1.110 0.24

TABLE 13 Three Month Stability Results - 40° C./75% RH Assay (mg/ LotReplicate Appearance pH mL) 1 1 Clear, colorless solution free ofvisible 3.21 1.01 particulate matter 2 Clear, colorless solution free ofvisible 3.23 1.01 particulate matter Mean (n = 2) 3.22 1.01 4 1 Clear,colorless solution free of visible 3.31 1.01 particulate matter 2 Clear,colorless solution free of visible 3.33 1.01 particulate matter Mean (n= 2) 3.32 1.01

TABLE 14 Three Month Related Substances Results - 40° C./75% RH UnknownMean of Total (Identified % Related Total Related Related Lot Replicateby RRT) Substance Substances (%) Substances (%) 1 1 0.039 0.06 0.23 0.170.364 0.06 0.555 0.11 2 0.555 0.10 0.10 4 1 0.039 0.08 0.25 0.20 0.3630.06 0.554 0.11 2 0.039 0.05 0.14 0.554 0.09

TABLE 15 Three Month Stability Results - 25° C./60% RH Assay (mg/ LotReplicate Appearance pH mL) 1 1 Clear, colorless solution free ofvisible 3.18 1.01 particulate matter 2 Clear, colorless solution free ofvisible 3.18 1.01 particulate matter Mean (n = 2) 3.18 1.01 4 1 Clear,colorless solution free of visible 3.21 1.01 particulate matter 2 Clear,colorless solution free of visible 3.19 1.01 particulate matter Mean (n= 2) 3.20 1.01

TABLE 16 Three Month Related Substances Results - 25° C./60% RH UnknownMean of Total (Identified % Related Total Related Related Lot Replicateby RRT) Substance Substances (%) Substances (%) 1 1 NR NR NR NR 2 NR NRNR 4 1 NR NR NR NR 2 NR NR NR

Medicament Delivery Devices

The naloxone compositions described herein can be included in anysuitable medicament delivery device. For example, in some embodiments, amedicament delivery device configured for self-administration (oradministration by an untrained user, such a person accompanying thepatient) can include any of the naloxone compositions described herein.Such medicament delivery devices can include, for example, anauto-injector, an intranasal delivery device, a pre-filled syringe, aninhaler or the like. In this manner, the medicament delivery device(including the naloxone composition) can be used by the patient (or anuntrained user) in any setting (e.g., the patient's home, in a publicvenue or the like).

In some embodiments, a medicament delivery device can be configured toautomatically deliver any of the naloxone compositions described herein.Similarly stated, in some embodiments, a medicament delivery device,after being actuated by the user, can automatically produce (i.e.,produce without any further human intervention) a force to deliver thenaloxone composition. In this manner, the force with which the naloxonecomposition is delivered is within a desired range, and is repeatablebetween different devices, users or the like.

One example of such a medicament delivery device is provided in FIG. 1,which is a schematic illustration of a medicament delivery device 1000according to an embodiment. The medicament delivery device 1000 includesa housing 1110, a medicament container 1400 and an energy storage member1570. The medicament container 1400 is disposed within the housing 1110,and contains (i.e., is filled or partially filled with) a naloxonecomposition 1420. The energy storage member 1570 is disposed within thehousing 1110, and is configured to produce a force F1 to deliver thenaloxone composition 1420 (e.g., from the medicament container 1400 to abody).

The naloxone composition 1420 can be any of the naloxone compositionsdescribed herein. In particular, the naloxone composition 1420 caninclude an effective amount of naloxone or salts thereof, atonicity-adjusting agent, and a pH adjusting agent. The naloxonecomposition 1420 can be formulated such that the osmolality of thenaloxone composition 1420 ranges from about 250-350 mOsm and the pHranges from about 3-5.

In some embodiments, the naloxone composition 1420 can include anysuitable concentration of 4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)morphinan-6-one. In some embodiments, for example, the naloxonecomposition 1420 has a concentration of4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)morphinan-6-one betweenapproximately 0.01 mg/mL and approximately 10 mg/mL. In otherembodiments, the naloxone composition 1420 has a concentration of4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)morphinan-6-one betweenapproximately 0.05 mg/mL and approximately 2 mg/mL.

The tonicity-adjusting agent can be any of the tonicity-adjusting agentsdescribed herein, and can be included within the naloxone composition1420 in any suitable amount and/or concentration. For example, in someembodiments, the tonicity-adjusting agent includes at least one ofdextrose, glycerin, mannitol, potassium chloride or sodium chloride. Inother embodiments, the tonicity-adjusting agent includes sodium chloridein an amount such that a concentration of sodium chloride is betweenapproximately 0.1 mg/mL and approximately 20 mg/mL.

The pH adjusting agent can be any of the pH adjusting agents describedherein, and can be included within the naloxone composition 1420 in anysuitable amount and/or concentration. For example, in some embodiments,the pH adjusting agent includes at least one of hydrochloric acid,citric acid, citrate salts, acetic acid, acetate salts, phosphoric acidor phosphate salts. In other embodiments, the pH adjusting agentincludes a dilute hydrochloric acid.

The medicament container 1400 can be any container suitable for storingthe naloxone composition 1420. In some embodiments, the medicamentcontainer 1400 can be, for example, a pre-filled syringe, a pre-filledcartridge, a vial, an ampule or the like. In other embodiments, themedicament container 1400 can be a container having a flexible wall,such as, for example, a bladder.

The energy storage member 1570 can be any suitable device or mechanismthat, when actuated, produces a force F1 to deliver the naloxonecomposition 1420. Similarly stated, the energy storage member 1570 canbe any suitable device or mechanism that produces the force F1 such thatthe naloxone composition 1420 is conveyed from the medicament container1400 into a body of a patient. The naloxone composition 1420 can beconveyed into a body via any suitable mechanism, such as, for example,by injection, intranasally, via inhalation or the like. By employing theenergy storage member 1570 to produce the force F1, rather than relyingon a user to manually produce the delivery force, the naloxonecomposition 1420 can be delivered into the body at the desired pressureand/or flow rate, and with the desired characteristics. Moreover, thisarrangement reduces the likelihood of partial delivery (e.g., that mayresult if the user is interrupted or otherwise rendered unable tocomplete the delivery).

In some embodiments, the energy storage member 1570 can be a mechanicalenergy storage member, such as a spring, a device containing compressedgas, a device containing a vapor pressure-based propellant or the like.In other embodiments, the energy storage member 1570 can be anelectrical energy storage member, such as a battery, a capacitor, amagnetic energy storage member or the like. In yet other embodiments,the energy storage member 1570 can be a chemical energy storage member,such as a container containing two substances that, when mixed, react toproduce energy.

As shown in FIG. 1, the energy storage member 1570 can be in anyposition and/or orientation relative to the medicament container 1400.In some embodiments, for example, the energy storage member 1570 can bepositioned within the housing 1110 spaced apart from the medicamentcontainer 1400. Moreover, in some embodiments, the energy storage member1570 can be positioned such that a longitudinal axis of the energystorage member 1570 is offset from the medicament container 1400. Inother embodiments, the energy storage member 1570 can substantiallysurround the medicament container 1400.

Moreover, the energy storage member 1570 can be operably coupled to themedicament container 1400 and/or the naloxone composition 1420 thereinsuch that the force F1 delivers the naloxone composition 1420. In someembodiments, for example, the force F1 can be transmitted to thenaloxone composition 1420 via a piston or plunger (not shown in FIG. 1).In other embodiments, the force F1 can be transmitted to the naloxonecomposition 1420 via a hydraulic or pneumatic coupling. In yet otherembodiments, the force F1 can be transmitted to the naloxone composition1420 electrically. In still other embodiments, the force F1 can betransmitted to the naloxone composition 1420 via a combination of any ofthe above.

In some embodiments, a medicament container can include an elastomericmember, such that the force produced by an energy storage member istransferred to the naloxone composition by the elastomeric member. Forexample, FIG. 2 is a schematic illustration of a medicament deliverydevice 2000 according to an embodiment. The medicament delivery device2000 includes a housing 2110, a medicament container 2400, anelastomeric member 2410 and an energy storage member 2570. Themedicament container 2400 is disposed within the housing 2110, andcontains (i.e., is filled or partially filled with) a naloxonecomposition 2420. The naloxone composition 2420 can be any of thenaloxone compositions described herein. The energy storage member 2570is disposed within the housing 2110, and is configured to produce aforce F2 to deliver the naloxone composition 2420, as described herein.

The elastomeric member 2410 is disposed within the medicament container2400 to seal an end portion of the medicament container 2400. Theelastomeric member 2410 can be disposed within the medicament container2400 during the fill process, and can form a substantially fluid-tightseal to prevent leakage of the naloxone composition 2420 from themedicament container 2400. Moreover, the elastomeric member 2410 isoperatively coupled to the energy storage member 2570 such that, in usethe force F2 acts upon the elastomeric member 2410 to deliver thenaloxone composition 2420 from the medicament container 2400.

The elastomeric member 2410 is formulated to be compatible with thenaloxone composition 2420. Similarly stated, the elastomeric member 2410is formulated to minimize any reduction in the efficacy of the naloxonecomposition 2420 that may result from contact (either direct orindirect) between the elastomeric member 2410 and the naloxonecomposition 2420. For example, in some embodiments, the elastomericmember 2410 can be formulated to minimize any leaching or out-gassing ofcompositions that may have an undesired effect on the naloxonecomposition 2420. In other embodiments, the elastomeric member 2410 canbe formulated to maintain its chemical stability, flexibility and/orsealing properties when in contact (either direct or indirect) withnaloxone over a long period of time (e.g., for up to six months, oneyear, two years, five years or longer).

In some embodiments, the elastomeric member 2410 can be formulated toinclude a polymer and a curing agent. In such embodiments, the polymercan include at least one of bromobutyl or chlorobutyl. In suchembodiments, the curing agent can include at least one of sulfur, zincor magnesium.

In some embodiments, the elastomeric member 2410 can be constructed frommultiple different materials. For example, in some embodiments, at leasta portion of the elastomeric member 2410 can be coated. Such coatingscan include, for example, polydimethylsiloxane. In some embodiments, atleast a portion of the elastomeric member 2410 can be coated withpolydimethylsiloxane in an amount of between approximately 0.02 mg/cm²and approximately 0.80 mg/cm².

A medicament delivery device configured for delivery of a naloxonecomposition can include an electronic circuit system that produces anoutput. Such output can include, for example, any output to assist theuser and/or patient in administering the dose of the naloxonecomposition. For example, FIG. 3 is a schematic illustration of amedicament delivery device 3000 according to an embodiment. Themedicament delivery device 3000 includes a housing 3110, a medicamentcontainer 3400, an elastomeric member 3410, an energy storage member3570 and an electronic circuit system 3900. The medicament container3400 is disposed within the housing 3110, and contains (i.e., is filledor partially filled with) a naloxone composition 3420. The naloxonecomposition 3420 can be any of the naloxone compositions describedherein. For example, in some embodiments, the naloxone composition 3420can include an effective amount of naloxone or salts thereof, atonicity-adjusting agent, and a pH adjusting agent. The naloxonecomposition can be formulated such that the osmolality of the naloxonecomposition ranges from about 250-350 mOsm and the pH ranges from about3-5.

The energy storage member 3570 is disposed within the housing 3110, andis configured to produce a force F2 to deliver the naloxone composition3420, as described herein. The elastomeric member 3410 is disposedwithin the medicament container 3400 to seal an end portion of themedicament container 3400. Moreover, the elastomeric member 3410 isoperatively coupled to the energy storage member 3570 such that, in usethe force F2 acts upon the elastomeric member 3410 to deliver thenaloxone composition 3420 from the medicament container 3400.

The electronic circuit system 3900 is configured to produce an outputOP1 when the electronic circuit system 3900 is actuated. The output canbe, for example, an audible or visual output related to the naloxonecomposition (e.g., an indication of the expiration date, the symptomsrequirement treatment with naloxone or the like), the use of themedicament delivery device, and/or post-administration procedures (e.g.,a prompt to call 911, instructions for the disposal of the device or thelike).

For example, in some embodiments, the electronic output OP1 can beassociated with an instruction for using the medicament delivery device3000. In other embodiments, the electronic output OP1 can be a post-useinstruction, such as, for example, a recorded message notifying the userthat the delivery of the naloxone composition 3420 is complete,instructing the user on post-use disposal of the medicament deliverydevice 3000 (e.g., post-use safety procedures), instructing the user toseek post-use medical treatment, and/or the like. In yet otherembodiments, the electronic output OP1 can be associated with thepatient's compliance in using medicament delivery device 3000.

The electronic output OP1 can be, for example, a visual output such as,for example, a text message to display on a screen (not shown), and/oran LED. In some embodiments, the electronic output OP1 can be an audiooutput, such as, for example, recorded speech, a series of tones, and/orthe like. In other embodiments, the electronic output OP1 can be awireless signal configured to be received by a remote device.

As described in more detail herein, the electronic circuit system 3900can include any suitable electronic components operatively coupled toproduce and/or output the electronic output OP1 and/or to perform thefunctions described herein. The electronic circuit system 3900 can besimilar to the electronic circuit systems described in U.S. Pat. No.7,731,686, entitled “Devices, Systems and Methods for MedicamentDelivery,” filed Jan. 9, 2007, which is incorporated herein by referencein its entirety.

The electronic circuit system 3900 can be actuated to produce theelectronic output OP1 in any suitable manner. For example, in someembodiments, the electronic circuit system 3900 can be associated withan actuation of the medicament delivery device 3000. Said another way,the electronic circuit system 3900 can be configured to output theelectronic output OP1 in response to actuation of the medicamentdelivery device 3000. In other embodiments, the electronic circuitsystem 3900 can be actuated manually by a switch (not shown in FIG. 3).Such a switch can be actuated (i.e., to actuated the electronic circuitsystem 3900) by a push button, by removing the medicament deliverydevice 3000 from a case or cover (not shown in FIG. 3), by receiving asignal from a remote electronic device, and/or any other suitablemechanism. In yet other embodiments, the electronic circuit system 3900can be actuated by receiving input from the user via a voice promptsystem.

The electronic circuit system 3900 can be coupled to and/or disposedwithin the housing 3110 in any suitable arrangement. For example, insome embodiments, the electronic circuit system 3900 can be coupled toan exterior or outer surface of the housing 3110. In other embodiments,at least a portion of the electronic circuit system 3900 can be disposedwithin the housing 3110. Moreover, in some embodiments, a portion of theelectronic circuit system 1900 is disposed within the housing 3110 suchthat the portion of the electronic circuit system 3900 is fluidicallyand/or physically isolated from the medicament container 3400.

The medicament delivery device 3000 can be any suitable device forautomatically delivering any of the naloxone compositions describedherein. In some embodiments, the medicament delivery device can be amedical injector configured to automatically deliver a naloxonecomposition. For example, FIGS. 4-42 show a medical injector 4000,according to an embodiment. FIGS. 4-5 are perspective views of themedical injector 4000 in a first configuration (i.e., prior to use). Themedical injector 4000 includes a housing 4110, a delivery mechanism 4500(see e.g., FIGS. 13-14), a medicament container 4400 containing analoxone composition 4420 (see e.g., FIG. 16), an electronic circuitsystem 4900 (see e.g., FIGS. 18-28), a cover 4200 (see e.g., FIGS.29-30), a safety lock 4700 (see e.g., FIGS. 31-34) and a system actuatorassembly 4300 (see e.g., FIGS. 13, 15, 35 and 36). A discussion of thecomponents of the medical injector 4000 will be followed by a discussionof the operation of the medical injector 4000.

As shown in FIGS. 6-12, the housing 4110 has a proximal end portion 4140and a distal end portion 4120. The housing 4110 defines a first statusindicator aperture 4150 and a second status indicator aperture 4151. Thefirst status indicator aperture 4150 defined by the housing 4110 islocated on a first side of the housing 4110, and the second statusindicator aperture 4151 of the housing 4110 is located on a second sideof the housing 4110. The status indicator apertures 4150, 4151 can allowa patient to monitor the status and/or contents of the medicamentcontainer 4400 contained within the housing 4110. For example, byvisually inspecting the status indicator apertures 4150, 4151, a patientcan determine whether the medicament container 4400 contains amedicament and/or whether a medicament has been dispensed.

As shown in FIGS. 10 and 11, the housing 4110 defines a gas cavity 4154,a medicament cavity 4157 and an electronic circuit system cavity 4153.The gas cavity 4154 has a proximal end portion 4155 and a distal endportion 4156. The gas cavity 4154 is configured to receive the gascontainer 4570 and a portion of the system actuator assembly 4300 (e.g.,the release member 4340 and the spring 4370, as shown in FIGS. 13 and14) as described in further detail herein. The proximal end portion 4155of the gas cavity 4154 is configured to receive the gas containerretention member 4580 of the proximal cap 4112 of the housing 4110, asdescribed in further detail herein. The gas cavity 4154 is in fluidcommunication with the medicament cavity 4157 via a gas passageway 4144(see e.g., FIG. 12), as described in further detail herein, and the gascavity 4154 is in fluid communication with a region outside the housing4110 via a safety lock aperture 4128 (see e.g., FIGS. 10 and 11).

The medicament cavity 4157 is configured to receive the medicamentcontainer 4400 and a portion of the delivery mechanism 4500. Inparticular, the carrier 4520 and the moveable member 4530 of themedicament delivery mechanism 4500 are movably disposed in themedicament cavity 4157. The medicament cavity 4157 is in fluidcommunication with a region outside the housing 4110 via a needleaperture 4122 (see e.g., FIGS. 10 and 11).

The electronic circuit system cavity 4153 is configured to receive theelectronic circuit system 4900. The housing 4110 has protrusions 4149(see e.g., FIG. 9) configured to stabilize the electronic circuit system4900 when the electronic circuit system 4900 is disposed within theelectronic circuit system cavity 4153. The housing 4110 also definesconnection apertures 4152 configured to receive connection protrusions4171 of the electronic circuit system 4900, and aperture 4145 (see e.g.,FIG. 7) configured to receive a portion of a protrusion 4174 of theelectronic circuit system 4900. In this manner, the electronic circuitsystem 4900 can be coupled to the housing 4110 within the electroniccircuit system cavity 4153. In other embodiments, the electronic circuitsystem 4900 can be coupled within the electronic circuit system cavity4153 by other suitable means such as an adhesive, a clip, a label and/orthe like.

The electronic circuit system cavity 4153 is fluidically and/orphysically isolated from the gas cavity 4154 and/or the medicamentcavity 4157 by a sidewall 4148. The sidewall 4148 can be any suitablestructure to isolate the electronic circuit system cavity 4153 withinthe housing 4110 from the gas cavity 4154 and/or the medicament cavity4157 within the housing 4110. Similarly, the gas cavity 4154 and themedicament cavity 4157 are separated by a sidewall 4146. In someembodiments, sidewall 4146 can be similar to the sidewall 4148, whichisolates the gas cavity 4154 and the medicament cavity 4157 from theelectronic circuit system cavity 4153. In other embodiments the gascavity 4154 can be fluidically and/or physically isolated from themedicament cavity 4157.

The proximal end portion 4140 of the housing 4110 includes a proximalcap 4112, a speaker protrusion 4147 (see e.g., FIGS. 9 and 10), andcover retention protrusions 4142 (see e.g., FIGS. 5 and 7). The speakerprotrusion 4147 is configured to maintain a position of an audio outputdevice 4956 of the electronic circuit system 4900 relative to thehousing 4110 when the electronic circuit system 4900 is attached to thehousing 4110, as described herein. Cover retention protrusions 4142 areconfigured to be received within corresponding openings 4215 on thecover 4200. In this manner, as described in more detail herein, thecover 4200 can be removably coupled to and disposed about at least aportion of the housing 4110.

As shown in FIG. 12, the proximal cap 4112 includes a gas containerretention member 4580 and defines a gas passageway 4144. The gascontainer retention member 4580 is configured to receive and/or retain agas container 4570 that can contain a pressurized gas. The gaspassageway 4144 is configured to allow for the passage of gas containedin the gas container 4570 from the gas cavity 4154 to the medicamentcavity 4157, as further described herein. Said another way, the gaspassageway 4144 places the gas cavity 4154 in fluid communication withthe medicament cavity 4157.

As shown in FIGS. 8 and 10, the distal end portion 4120 of the housing4110 defines a battery isolation protrusion aperture 4121, a needleaperture 4122, a safety lock actuator groove 4123, a safety lockaperture 4128, a base actuator groove 4124, base retention recesses4125A, 4125B, and base rail grooves 4127. The battery isolationprotrusion aperture 4121 is configured to receive the battery isolationprotrusion 4235 of the cover 4200 (see e.g., FIG. 30), as described infurther detail herein.

The needle aperture 4122 is configured to allow the needle 4452 (seee.g., FIGS. 13, 39 and 40) to exit the housing 4110 when the medicalinjector 4000 is actuated. The portion of the sidewall of the housing4110 that defines the needle aperture 4122 includes multiple sheathretention protrusions 4126. In some embodiments, the sheath retentionprotrusions can interact with a plurality of ribs 4728 of the needlesheath 4720 (see e.g. FIG. 34) to maintain a position of the needlesheath 4720 relative to the safety lock 4700 when the safety lock 4700is coupled to the housing 4110 and/or when the safety lock 4700 is beingremoved from the housing 4110.

The safety lock actuator groove 4123 is configured to receive anactuator 4744 of the safety lock 4700. As described in more detailherein, the actuator 4744 is configured to engage and/or activate theelectronic circuit system 4900 when the safety lock 4700 is moved withrespect to the housing 4110. The safety lock aperture 4128 is configuredto receive a safety lock protrusion 4742 (see e.g., FIGS. 30 and 31). Asdescribed in more detail below, when the medical injector is in thefirst configuration (i.e., when the safety lock 4700 is in place priorto use), the safety lock protrusion 4742 is disposed within an opening4346 between extensions 4343 of a release member 4340 (see e.g., FIGS.14 and 15) such that activation of the medical injector 4000 isprevented. The safety lock 4700, its components and functions arefurther described herein.

The distal base retention recesses 4125A are configured to receive thebase connection knobs 4358 of the actuator 4302 (also referred to hereinas “base 4302,” see e.g., FIG. 35) when the base 4302 is in a firstposition relative to the housing 4110. The proximal base retentionrecesses 4125B are configured to receive the base connection knobs 4358of the base 4302 when the base 4302 is in a second position relative tothe housing 4110. The base retention recesses 4125A, 4125B have atapered proximal sidewall and a non-tapered distal sidewall. This allowsthe base retention recesses 4125A, 4125B to receive the base connectionknobs 4358 such that the base 4302 can move proximally relative to thehousing 4110, but cannot move distally relative to the housing 4110.Said another way, the distal base retention recesses 4125A areconfigured to prevent the base 4302 from moving distally when the base4302 is in a first position and the proximal base retention recesses4125B are configured to prevent the base 4302 from moving distally whenthe base 4302 is in a second position. Similarly stated, the proximalbase retention recesses 4125B and the base connection knobs 4358cooperatively prevent “kickback” after the medical injector 4000 isactuated.

The base actuator groove 4124 is configured to receive an actuator 4311of the base 4302. As described in more detail herein, the actuator 4311of the base 4302 is configured to engage the electronic circuit system4900 when the base 4302 is moved with respect to the housing 4110. Thebase rail grooves 4127 are configured to receive the guide members 4312of the base 4302. The guide members 4312 of the base 4302 and the baserail grooves 4127 of the housing 4110 engage each other in a way thatallows the guide members 4312 of the base 4302 to slide in a proximaland/or distal direction within the base rail grooves 4127 while limitinglateral movement of the guide members 4312. This arrangement allows thebase 4302 to move in a proximal and/or distal direction with respect tothe housing 4110 but prevents the base 4302 from moving in a lateraldirection with respect to the housing 4110.

FIGS. 13-16 show the medicament container 4400, the system actuatorassembly 4300 and the medicament delivery mechanism 4500 of the medicalinjector 4000. The medical injector 4000 is similar to theauto-injectors described in U.S. Pat. No. 7,648,482, entitled “Devices,Systems and Methods for Medicament Delivery,” filed Nov. 21, 2006, whichis incorporated herein by reference in its entirety.

The medicament container 4400 of the medicament delivery mechanism 4500has a distal end portion 4402 and a proximal end portion 4404, andcontains (i.e., is filled with or partially filled with) a naloxonecomposition 4420 (see, e.g., FIG. 16). The distal end portion 4402 ofthe medicament container 4400 contains a seal 4406. The seal 4406, whichcan be, for example, an 8-I crimp seal, is configured to burst whenpunctured by the proximal end 4456 of the needle 4452, as describedbelow. The proximal end portion 4404 of the medicament container 4400includes an elastomeric member 4410, and is configured to receive apiston portion 4534 of the movable member 4530. Although the medicamentcontainer 4400 is shown in FIG. 16 as including a liner 4407, in otherembodiments, the medicament container 4400 need not include the liner4407.

The medicament container 4400 can have any suitable size (e.g., lengthand/or diameter) and can contain any suitable volume of the naloxonecomposition 4420. Moreover, the medicament container 4400 and themovable member 4530 can be collectively configured such that the movablemember 4530 travels a desired distance within the medicament container4400 (i.e., the “stroke”) during an injection event. In this manner, themedicament container 4400, the volume of the naloxone composition 4420within the medicament container 4400 and the movable member 4530 can becollectively configured to provide a desired fill volume and deliveryvolume. In some embodiments, for example, the size of the medicamentcontainer 4400 and the length of the movable member 4530 can be suchthat the fill volume of the naloxone composition 4420 is approximately0.76 ml and the delivery volume of the naloxone composition 4420 isapproximately 0.30 ml (providing a delivery volume to fill volume ratioof approximately 0.4). In other embodiments, for example, the size ofthe medicament container 4400 and the length of the movable member 4530can be such that the fill volume of the naloxone composition 4420 isapproximately 0.66 ml and the delivery volume of the naloxonecomposition 4420 is approximately 0.40 ml (providing a delivery volumeto fill volume ratio of approximately 0.6).

Moreover, the length of the medicament container 4400 and the length ofthe movable member 4530 can be configured such that the medicamentdelivery mechanism 4500 can fit in the same housing 4110 regardless ofthe fill volume, the delivery volume and/or the ratio of the fill volumeto the delivery volume. In this manner, the same housing and productiontooling can be used to produce devices having various dosages of thenaloxone composition. For example, in a first embodiment (e.g., having afill volume to delivery volume ratio of 0.4), the medicament containerhas a first length and the movable member has a first length. In asecond embodiment (e.g., having a fill volume to delivery volume ratioof 0.6), the medicament container has a second length shorter than thefirst length, and the movable member has a second length longer than thefirst length. In this manner, the stroke of the device of the secondembodiment is longer than that of the device of the first embodiment,thereby allowing a greater dosage. The medicament container of thedevice of the second embodiment, however, is shorter than the medicamentcontainer of the device of the first embodiment, thereby allowing thecomponents of both embodiments to be disposed within the same housingand/or a housing having the same length.

The naloxone composition 4420 contained within the medicament container4400 can be any of the naloxone compositions described herein. Inparticular, the naloxone composition 4420 can include an effectiveamount of naloxone or salts thereof, a tonicity-adjusting agent, and apH adjusting agent. The naloxone composition 4420 can be formulated suchthat the osmolality of the naloxone composition 4420 ranges from about250-350 mOsm and the pH ranges from about 3-5.

In some embodiments, the naloxone composition 4420 can include anysuitable concentration of 4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)morphinan-6-one. In some embodiments, for example, the naloxonecomposition 4420 has a concentration of4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)morphinan-6-one betweenapproximately 0.01 mg/mL and approximately 10 mg/mL. In otherembodiments, the naloxone composition 4420 has a concentration of4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)morphinan-6-one betweenapproximately 0.05 mg/mL and approximately 2 mg/mL.

The tonicity-adjusting agent can be any of the tonicity-adjusting agentsdescribed herein, and can be included within the naloxone composition4420 in any suitable amount and/or concentration. For example, in someembodiments, the tonicity-adjusting agent includes at least one ofdextrose, glycerin, mannitol, potassium chloride or sodium chloride. Inother embodiments, the tonicity-adjusting agent includes sodium chloridein an amount such that a concentration of sodium chloride is betweenapproximately 0.1 mg/mL and approximately 20 mg/mL.

The pH adjusting agent can be any of the pH adjusting agents describedherein, and can be included within the naloxone composition 4420 in anysuitable amount and/or concentration. For example, in some embodiments,the pH adjusting agent includes at least one of hydrochloric acid,citric acid, citrate salts, acetic acid, acetate salts, phosphoric acidor phosphate salts. In other embodiments, the pH adjusting agentincludes a dilute hydrochloric acid.

The elastomeric member 4410 can be of any design or formulation suitablefor contact with the naloxone composition 4420. For example, theelastomeric member 4410 can be formulated to minimize any reduction inthe efficacy of the naloxone composition 4420 that may result fromcontact (either direct or indirect) between the elastomeric member 4410and the naloxone composition 4420. For example, in some embodiments, theelastomeric member 4410 can be formulated to minimize any leaching orout-gassing of compositions that may have an undesired effect on thenaloxone composition 4420. In other embodiments, the elastomeric member4410 can be formulated to maintain its chemical stability, flexibilityand/or sealing properties when in contact (either direct or indirect)with naloxone over a long period of time (e.g., for up to six months,one year, two years, five years or longer).

In some embodiments, the elastomeric member 4410 can be formulated toinclude a polymer and a curing agent. In such embodiments, the polymercan include at least one of bromobutyl or chlorobutyl. In suchembodiments, the curing agent can include at least one of sulfur, zincor magnesium.

In some embodiments, the elastomeric member 4410 can be constructed frommultiple different materials. For example, in some embodiments, at leasta portion of the elastomeric member 4410 can be coated. Such coatingscan include, for example, polydimethylsiloxane. In some embodiments, atleast a portion of the elastomeric member 4410 can be coated withpolydimethylsiloxane in an amount of between approximately 0.02 mg/cm²and approximately 0.80 mg/cm².

As shown in FIG. 13, the system actuator 4300 includes the base 4302, arelease member 4340 and a spring 4370. FIG. 14 shows certain of theinternal components of the medical injector 4000 without the base 4302and the spring 4370 so that the release member 4340 can be more clearlyshown.

The release member 4340 has a proximal end portion 4342 and a distal endportion 4344, and is movably disposed within the distal end portion 4156of the gas cavity 4154. The proximal end portion 4342 of the releasemember 4340 includes a sealing member 4345 and a puncturer 4341. Thesealing member 4345 is configured to engage the sidewall of the housing4110 defining the gas cavity 4154 such that the proximal end portion4155 of the gas cavity 4154 is fluidically isolated from the distal endportion 4156 of the gas cavity 4154. In this manner, when gas isreleased from the gas container 4570, the gas contained in the proximalend portion 4155 of the gas cavity 4154 is unable to enter the distalend portion 4156 of the gas cavity 4154. The puncturer 4341 of theproximal end portion 4342 of the release member 4340 is configured tocontact and puncture a frangible seal 4573 on the gas container 4570when the release member 4340 moves proximally within the gas cavity4154, as shown by the arrow BB in FIG. 14.

The distal end portion 4344 of the release member 4340 includesextensions 4343. The extensions 4343 include projections 4347 thatinclude tapered surfaces 4349 and engagement surfaces 4348. Further, theextensions 4343 define an opening 4346 between the extensions 4343. Theengagement surfaces 4348 of the projections 4347 are configured toextend through the safety lock aperture 4128 of the housing 4110 andcontact a distal surface of the housing 4110, as shown in FIG. 15. Inthis manner, the engagement surfaces 4348 of the projections 4347 limitproximal movement of the release member 4340 when the engagementsurfaces 4348 are in contact with the distal surface of the housing4110.

The opening 4346 defined by the extensions 4343 is configured to receivethe safety lock protrusion 4742 of the safety lock 4700 (see e.g., FIGS.15 and 27). The safety lock protrusion 4742 is configured to prevent theextensions 4343 from moving closer to each other. Said another way, thesafety lock protrusion 4742 is configured to ensure that the extensions4343 remain apart and the engagement surfaces 4348 of the projections4347 remain in contact with the distal end portion 4120 of the housing4110. In some embodiments, for example, the release member 4340 and/orthe extensions 4343 can be constructed from any suitable materialconfigured to withstand deformation that may occur when exposed to aload over an extended period of time. In some embodiments, for example,the release member 4340 and/or the extensions 4343 can be constructedfrom brass.

The tapered surfaces 4349 of the projections 4347 are configured tocontact protrusions 4313 on a proximal surface 4310 of the base 4302(see e.g., FIG. 35) when the base 4302 is moved proximally relative tothe housing 4110. Accordingly, when the base 4302 is moved proximallyrelative to the housing 4110, the extensions 4343 are moved together bythe contact protrusions 4313. The inward movement of the extensions 4343causes the release member 4340 to become disengaged from the distal endportion of the housing 4110, thereby allowing the release member 4340 tobe moved proximally along its longitudinal axis as the spring 4370expands.

The medicament delivery mechanism 4500 includes a gas container 4570, acarrier 4520, a movable member 4530, and a retraction spring 4590. Asdescribed above, the carrier 4520 and the movable member 4530 aredisposed within the medicament cavity 4157 of the housing 4110. The gascontainer 4570 is disposed within the gas cavity 4154 of the housing4110.

The gas container 4570 includes a distal end portion 4572 and a proximalend portion 4576, and is configured to contain a pressurized gas. Thedistal end portion 4572 of the gas container 4570 contains a frangibleseal 4573 configured to break when the puncturer 4341 of the proximalend portion 4342 of the release member 4340 contacts the frangible seal4573. The gas container retention member 4580 of the proximal cap 4112of the housing 4110 is configured to receive and/or retain the proximalend portion 4576 of the gas container 4570. Said another way, theposition of the gas container 4570 within the gas cavity 4154 ismaintained by the gas container retention member 4580.

The movable member 4530 of the medicament delivery mechanism 4500 ismovably disposed within the medicament cavity 4157. The movable member4530 includes a piston portion 4534 having a plunger at the distal endportion of the piston portion 4534. The piston portion 4534 isconfigured to move within the medicament container 4400. In this manner,the piston portion 4534 of the movable member 4530 can apply a force tothe elastomeric member 4410 to convey the naloxone composition 4420contained in the medicament container 4400. The piston portion 4534 canbe constructed of a resilient, durable, and/or sealing material, such asa rubber.

The carrier 4520 of the medicament delivery mechanism 4500 includes adistal end portion 4522 and a proximal end portion 4526. The medicamentcontainer 4400 is coupled to the carrier 4520 via a “snap-fit”connection (not shown) such that the medicament container 4400 can moverelative to the carrier 4520 between a first configuration and a secondconfiguration during an injection event. In the first configuration, thecarrier 4520 is configured to move within the medicament cavity 4157such that movement of the carrier 4520 within the medicament cavity 4157causes contemporaneous movement of the medicament container 4400 withinthe medicament cavity 4157. The proximal end portion 4456 of the needle4452 is spaced apart from the seal 4406 of the medicament container 4400when the carrier 4520 and the medicament container 4400 are collectivelyin the first configuration (e.g., during needle insertion). When thecarrier 4520 and the medicament container 4400 are moved to the secondconfiguration, the medicament container 4400 releases from the“snap-fit” causing the medicament container 4400 to move distally withrespect to the carrier 4520, causing the proximal end portion 4456 ofthe needle 4452 to pierce the seal 4406. In this manner, the needle 4452can be selectively placed in fluid communication with the medicamentcontainer 4400 to define a medicament delivery path (not shown).

As shown in FIGS. 13, 14 and 41, the proximal end portion 4526 of thecarrier 4520 includes a gas valve actuator 4527. The gas valve actuator4527 is configured to engage a gas relief valve (not shown) of themovable member 4530 to allow the pressurized gas contained within thegas chamber (i.e., the volume within the medicament cavity 4157 betweenthe proximal end of the housing 4110 and the proximal end of the movablemember 5530) to escape when the injection event is complete. Thus, afterthe gas pressure within the medicament cavity 4157 decreases below acertain level, the force exerted by the retraction spring 4590 on thecarrier 4520 can be sufficient to cause the carrier 4520 to moveproximally within the housing 4110 (i.e., to retract). In addition, thisarrangement results in there being substantially no residual forcewithin the housing, which decreases stress on the components after theinjection event.

FIGS. 18-28 show the electronic circuit system 4900. The electroniccircuit system 4900 of the medical injector 4000 includes an electroniccircuit system housing 4170, a printed circuit board 4922, a batteryassembly 4962, an audio output device 4956, two light emitting diodes(LEDs) 4958A, 4958B and a battery clip 4910. As shown in FIG. 25, theelectronic circuit system 4900 is configured to fit within theelectronic circuit system cavity 4153 of the housing 4110. Accordingly,as described above, the electronic circuit system 4900 is physicallyand/or fluidically isolated from the medicament cavity 4157, the gascavity 4154 and/or the medicament delivery device 4500. As describedherein, the electronic circuit system 4900 is configured to output anelectronic output associated with the use of the medical injector 4000.

The electronic circuit system housing 4170 of the electronic circuitsystem 4900 includes a distal end portion 4180 and a proximal endportion 4190. The proximal end portion 4190 includes connectionprotrusions 4171A and a battery clip protrusion 4173. The connectionprotrusions 4171A extend from the proximal end portion 4190 of theelectronic circuit system housing 4170, and are configured to bedisposed within the connection apertures 4152 of the housing 4110, asdescribed above. In this manner, the electronic circuit system 4900 canbe coupled to the housing 4110 within the electronic circuit systemcavity 4153. In other embodiments, the electronic circuit system 4900can be coupled to the housing 4110 by other suitable means such as anadhesive, a clip, a label and/or the like. As described in more detailherein, the battery clip protrusion 4173 is configured to hold thebattery clip 4910 in place.

The proximal end portion 4190 of the electronic circuit system housing4170 defines multiple sound apertures 4191. The audible output device4956 is disposed against the proximal end portion 4190 of the electroniccircuit system housing 4170 such that the front face of the audibleoutput device 4956 is disposed adjacent the sound apertures 4191. Inthis manner, the sound apertures 4191 are configured to allow sound froman audio output device 4956 to pass from the audio output device 4956 toa region outside of the housing 4110.

As shown in FIGS. 21 and 22, the distal end portion 4180 of theelectronic circuit system housing 4170 includes a connection protrusion4171B, a stiffening protrusion 4174, and defines an LED aperture 4181,an aperture 4172, a safety lock actuator groove 4182, and a baseactuator groove 4183. The LED aperture 4181 is configured to receive theLEDs 4958A, 4958B such that a user can view the LEDs 4958A, 4958B, whichare described in more detail herein.

The connection protrusion 4171B extends from the distal end portion 4180of the electronic circuit system housing 4170, and is configured toattach the electronic circuit system 4900 to the housing 4110, asdescribed above. The stiffening protrusion 4174 is configured to have atleast a portion received within and/or accessible via the aperture 4145in the housing 4110 (see e.g., FIG. 7). The stiffening protrusion 4174is configured to limit the bending (e.g., buckling) of the electroniccircuit system housing 4170 when the electronic circuit system housing4170 is coupled to the housing 4110. Moreover, a user can access thestiffening protrusion 4174 via the aperture 4172. In this manner, forexample, the user can disengage the stiffening protrusion 4174 from theaperture 4145.

The safety lock actuator groove 4182 of the electronic circuit systemhousing 4170 is configured to be disposed adjacent the safety lockactuator groove 4123 of the distal end portion 4120 of the housing 4110.In this manner, the safety lock actuator groove 4182 of the electroniccircuit system housing 4170 and the safety lock actuator groove 4123 ofthe distal end portion 4120 of the housing 4110 collectively receive theactuator 4744 of the safety lock 4700, which is described in more detailherein. Similarly, the base actuator groove 4183 of the electroniccircuit system housing 4170 is configured to be disposed about the baseactuator groove 4124 of the distal end portion 4120 of the housing 4110.The base actuator groove 4183 of the electronic circuit system housing4170 and the base actuator groove 4124 of the distal end portion 4120 ofthe housing 4110 collectively receive the actuator 4311 of the base4302, which is described in more detail herein.

The printed circuit board 4922 of the electronic circuit system 4900includes a substrate 4924, a first actuation portion 4926 and a secondactuation portion 4946. The substrate 4924 of the printed circuit board4922 includes the electrical components necessary for the electroniccircuit system 4900 to operate as desired. For example, the electricalcomponents can be resistors, capacitors, inductors, switches,microcontrollers, microprocessors and/or the like. The printed circuitboard may also be constructed of materials other than a flexiblesubstrate such as a FR4 standard board (rigid circuit board).

As shown in FIGS. 26-28, the first actuation portion 4926 includes afirst electrical conductor 4934 and defines an opening 4928 having aboundary 4929. The opening 4928 of the first actuation portion 4926 isconfigured to receive a protrusion 4746 of the actuator 4744 of thesafety lock 4700. The boundary 4929 of the first opening 4928 has adiscontinuous shape, such as, for example, a teardrop shape, thatincludes a stress concentration riser 4927. The discontinuity and/or thestress concentration riser 4927 of the boundary 4929 can be of anysuitable shape to cause the substrate 4924 to deform in a predetermineddirection when the protrusion 4746 of the actuator 4744 of the safetylock 4700 is moved relative to the opening 4928, as shown by the arrowCC in FIG. 27.

The opening 4928 is defined adjacent the first electrical conductor 4934that electronically couples the components included in the electroniccircuit system 4900. The first electrical conductor 4934 includes afirst switch 4972, which can be, for example a frangible portion of thefirst electrical conductor 4934. In use, when the safety lock 4700 ismoved from a first position (see e.g., FIG. 26) to a second position(see e.g., FIG. 27), the actuator 4744 moves in a directionsubstantially parallel to a plane defined by a surface of the firstactuation portion 4926 of the substrate 4924. The movement of theactuator 4744 causes the protrusion 4746 to move within the firstopening 4928, as indicated by the arrow CC in FIG. 27. The movement ofthe protrusion 4746 tears the first actuation portion 4926 of thesubstrate 4924, thereby separating the portion of the first electricalconductor 4934 including the first switch 4972. Said another way, whenthe safety lock 4700 is moved from its first position to its secondposition (see e.g., FIG. 38), the actuator 4744 moves irreversibly thefirst switch 4972 from a first state (e.g., a state of electricalcontinuity) to a second state (e.g., a state of electricaldiscontinuity). Said yet another way, when the safety lock 4700 is movedfrom its first position to its second position, the actuator 4744disrupts the first electrical conductor 4934.

The second actuation portion 4946 includes a second electrical conductor4935 and defines an opening 4945, having a boundary 4949 and a tearpropagation limit aperture 4948. As shown in FIGS. 25-28, the opening4945 of the second actuation portion 4946 is configured to receive aportion of an actuator 4311 of the base 4302. The boundary 4949 of theopening 4945 has a discontinuous shape that includes a stressconcentration riser 4947. The discontinuity and/or the stressconcentration riser 4947 of the boundary 4949 can be of any suitableshape to cause the substrate 4924 to deform in a predetermined directionwhen the actuator 4311 of the base 4302 is moved in a proximal directionrelative to the opening 4945, as shown by the arrow DD in FIG. 23.

The second electrical conductor 4935 includes a second switch 4973disposed between the opening 4945 and the tear propagation limitaperture 4948, which can be, for example, a frangible portion of thesecond electrical conductor 4935. In use, when the base 4302 is movedfrom its first position to its second position (see e.g., FIG. 39), theactuator 4311 moves in a proximal direction, substantially parallel to aplane defined by a surface of the second actuation portion 4946 of thesubstrate 4924. The proximal movement of the actuator 4311 tears thesecond actuation portion 4946 of the substrate 4924, thereby separatingthe portion of the second electrical conductor 4935 including the secondswitch 4973. Said another way, when the base 4302 is moved from itsfirst position to its second position, the actuator 4311 movesirreversibly the second switch 4973 from a first state (e.g., a state ofelectrical continuity) to a second state (e.g., a state of electricaldiscontinuity). The tear propagation limit aperture 4948 is configuredto limit the propagation of the tear in the substrate 4924 in theproximal direction. Said another way, the tear propagation limitaperture 4948 is configured to ensure that the tear in the substrate4924 does not extend beyond the tear propagation limit aperture 4948.The tear propagation limit aperture 4948 can be any shape configured tostop the propagation of a tear and/or disruption of the substrate 4924.For example, the tear propagation limit aperture 4948 can be ovalshaped. In other embodiments, the proximal boundary of the tearpropagation limit aperture 4948 can be reinforced to ensure that thetear in the substrate 4924 does not extend beyond the tear propagationlimit aperture 4948.

In some embodiments, the safety lock 4700 and base 4302 can beconfigured to interact with mechanical and/or optical switches toproduce an electronic output in a reversible manner.

The battery assembly 4962 of the electronic circuit system 4900 includestwo batteries stacked on top of one another. In other embodiments, theelectronic circuit system can include any number of batteries and/or anysuitable type of power source. In some embodiments, for example, thebattery assembly can include Lithium batteries such as, for example,CR1616, CR2016s, type AAA or the like. The battery assembly 4962 has afirst surface 4964 and a second surface 4966. The first surface 4964 ofthe battery assembly 4962 can contact an electrical contact (not shown)disposed on the substrate 4924. The second surface 4966 of the batteryassembly 4962 is configured to contact a contact portion 4918 of adistal end portion 4916 of a battery clip 4910. When both the electricalcontact of the substrate 4924 and the contact portion 4918 of the distalend portion 4916 of the battery clip 4910 contact the battery assembly4962, the batteries of the battery assembly 4962 are placed inelectrical communication with the electronic circuit system 4900. Saidanother way, when the electrical contact of the substrate 4924 and thecontact portion 4918 of the distal end portion 4916 of the battery clip4910 contact the battery assembly 4962, the battery assembly 4962 isconfigured to supply power to the electronic circuit system 4900.

The battery clip 4910 (shown in FIG. 23) includes a proximal end portion4912 and a distal end portion 4916. The proximal end portion 4912defines a retention aperture 4913. The retention aperture 4913 isconfigured to receive the battery clip protrusion 4173 of the electroniccircuit system housing 4170. In this manner, the battery clip protrusion4173 maintains the position of the battery clip 4910 with respect to theelectronic circuit system housing 4170 and/or the battery assembly 4962.

The distal end portion 4916 of the battery clip 4910 includes a contactportion 4918 and an angled portion 4917. As described above, the contactportion 4918 is configured to contact the second surface 4966 of thebattery assembly 4962 to place the battery assembly 4962 in electricalcommunication with the electronic circuit system 4900. The angledportion 4917 of the distal end portion 4916 of the battery clip 4910 isconfigured to allow a proximal end portion 4236 of a battery isolationprotrusion 4235 (see e.g., FIG. 30) to be disposed between the secondsurface 4966 of the battery assembly 4962 and the contact portion 4918of the distal end portion 4916 of the battery clip 4910. When thebattery isolation protrusion 4235 is disposed between the second surface4966 of the battery assembly 4962 and the contact portion 4918 of thedistal end portion 4916 of the battery clip 4910, the electrical pathbetween the battery assembly 4962 and the remainder of the electricalcircuit system 4900 is severed, thereby removing power from theelectronic circuit system 4900. The contact portion 4918 of the distalend portion 4916 of the battery clip 4910 is biased such that when thebattery isolation protrusion 4235 is removed, the contact portion 4918will move into contact the second surface 4966 of the battery assembly4962, thereby restoring electrical communication between the batteryassembly 4962 and the electronic circuit system 4900. In someembodiments, the battery isolation protrusion 4235 can be repeatedlyremoved from between the second surface 4966 of the battery assembly4962 and the contact portion 4918 of the distal end portion 4916 of thebattery clip 4910 and reinserted. Said another way, the batteryisolation protrusion 4235 and the battery clip 4910 collectively form areversible on/off switch.

The audio output device 4956 of the electronic circuit system 4900 isconfigured to output audible sound to a user in response to a use of themedical injector 4000. In some embodiments, the audible output device4956 can be a speaker. In some embodiments, the audible sound can be,for example, associated with a recorded message and/or a recordedspeech. In other embodiments, the audible instructions can be an audiblebeep, a series of tones and/or or the like.

In other embodiments, the medical injector 4000 can have a networkinterface device (not shown) configured to operatively connect theelectronic circuit system 4900 to a remote device (not shown) and/or acommunications network (not shown). In this manner, the electroniccircuit system 4900 can send information to and/or receive informationfrom the remote device. The remote device can be, for example, a remotecommunications network, a computer, a compliance monitoring device, acell phone, a personal digital assistant (PDA) or the like. Such anarrangement can be used, for example, to download replacementprocessor-readable code from a central network to the electronic circuitsystem 4900. In some embodiments, for example, the electronic circuitsystem 4900 can download information associated with a medical injector4000, such as an expiration date, a recall notice, updated useinstructions or the like. Similarly, in some embodiments, the electroniccircuit system 4900 can upload compliance information associated withthe use of the medical injector 4000 via the network interface device.

FIGS. 24 and 25 show the cover 4200 of the medical injector 4000. Thecover 4200 includes a proximal end portion 4210 and a distal end portion4230, and defines a cavity 4242. The cavity 4242 of the cover 4200 isconfigured to receive at least a portion of the housing 4110. Thus, whenthe portion of the housing 4110 is disposed within the cover 4200, thecover 4200 blocks an optical pathway between the medicament container4400 and a region outside of the housing 4110. Similarly stated, whenthe portion of the housing 4110 is disposed within the cover 4200, thecover 4200 is obstructs the first status indicator aperture 4150 and/orthe second status indicator aperture 4151 of the housing 4110 to reducethe amount of light transmitted to the naloxone composition 4420 withinthe medicament container 4400. In this manner, the life of the naloxonecomposition 4420 can extended by the prevention and/or reduction ofdegradation to the naloxone that may be caused by ultra-violetradiation.

The proximal end portion 4210 of the cover 4200 defines apertures 4215configured to receive the cover retention protrusions 4142 of thehousing 4110 (shown in FIGS. 5 and 7). In this manner, the apertures4215 and the cover retention protrusions 4142 of the housing 4110removably retain the cover 4200 about at least a portion of the housing4110. Said another way, the apertures 4215 and the cover retentionprotrusions 4142 of the housing 4110 are configured such that the cover4200 can be removed from a portion of the housing 4110 and then replacedabout the portion of the housing 4110.

As described above, the electronic circuit system 4900 can be actuatedwhen the housing 4110 is at least partially removed from the cover 4200.More particularly, the distal end portion 4230 of the cover 4200includes a battery isolation protrusion 4235. The battery isolationprotrusion 4235 includes a proximal end portion 4236 and a taperedportion 4237. The proximal end portion 4236 of the battery isolationprotrusion 4235 is configured to be removably disposed between thesecond surface 4966 of the battery assembly 4962 and the contact portion4918 of the distal end portion 4916 of the battery clip 4910, asdescribed above.

FIGS. 31-34 show the safety lock 4700 of the medical injector 4000. Thesafety lock 4700 of the medical injector 4000 includes a proximalsurface 4740, a distal surface 4760 opposite the proximal surface 4740and a needle sheath 4720. The safety lock 4700 defines a needle sheathaperture 4770 and a battery isolation protrusion aperture 4775. Thebattery isolation protrusion aperture 4775 is configured to receive thebattery isolation protrusion 4235 of the cover 4200 such that thebattery isolation protrusion 4235 can be disposed within the electroniccircuit system cavity 4153 or the electronic circuit system 4900, asdescribed above. Similarly stated, the battery isolation protrusionaperture 4775 of the safety lock 4700 is aligned with the batteryisolation protrusion aperture 4121 of the housing 4110, such that thebattery isolation protrusion 4235 can be disposed within the electroniccircuit system cavity 4153 when the cover 4200 is disposed about aportion of the housing 4110.

The proximal surface 4740 of the safety lock 4700 includes a safety lockprotrusion 4742, a stopper 4743, an actuator 4744 and two opposing pulltabs 4741. As described above, when the safety lock 4700 is in a first(locked) position, the safety lock protrusion 4742 is configured to bedisposed in the opening 4346 defined by the extensions 4343 of thedistal end portion 4344 of the release member 4340 (see also FIG. 15).Accordingly, the safety lock protrusion 4742 is configured to preventthe extensions 4343 from moving closer to each other, thereby preventingproximal movement of the release member 4340 of the medicament deliverymechanism 4500 and/or delivery of the naloxone composition 4420. Thestopper 4743 of the safety lock 4700 is a protrusion extending from theproximal surface 4740 of the safety lock 4700. The stopper 4743 isconfigured to contact a portion of the housing 4110 to limit theproximal movement of the safety lock 4700 relative to the housing 4110.In other embodiments, the stopper 4743 can be any structure configuredto limit the proximal movement of the safety lock 4700.

The actuator 4744 of the safety lock 4700 has an elongated portion 4745and a protrusion 4746. The elongated portion 4745 extends in a proximaldirection from the proximal surface 4740. In this manner, the elongatedportion 4745 can extend through a safety lock actuator opening 4356 ofthe base 4302 (see e.g., FIG. 35) and within the safety lock actuatorgroove 4123 of the housing 4110 and the safety lock actuator groove 4182of the electronic circuit system housing 4170. The protrusion 4746extends in a direction substantially transverse to the elongated portion4745 and/or substantially parallel to the proximal surface 4740 of thesafety lock 4700. As described above, the opening 4928 of the firstactuation portion 4926 is configured to receive the protrusion 4746 ofthe actuator 4744 of the safety lock 4700.

The pull tabs 4741 of the safety lock 4700 include a grip portion 4747and indicia 4748. The grip portion 4747 of the pull tabs 4741 providesan area for the user to grip and/or remove the safety lock 4700 from therest of the medicament delivery system 4700. The indicia 4748 providesinstruction on how to remove the safety lock 4700. In some embodiments,for example, the indicia 4748 can indicate the direction the user shouldpull the safety lock 4700 to remove the safety lock 4700.

As shown in FIG. 33, the needle sheath 4720 of the safety lock 4700includes a distal end portion 4724, a proximal end portion 4722 and aplurality of ribs 4728. The needle sheath 4720 can also define a lumen4729. The lumen 4729 of the safety lock 4700 is configured to receivethe needle 4452. In this manner, the needle sheath 4720 can protect theuser from the needle 4452 and/or can keep the needle 4452 sterile beforethe user actuates the medical injector 4000. The proximal end portion4722 of the needle sheath is configured to contact the distal endportion 4522 of the carrier 4520 of the medicament delivery mechanism4500.

The distal end portion 4724 of the needle sheath 4720 has an angledridge 4725. The angled ridge 4725 is configured to allow the proximalend portion 4722 of the needle sheath 4720 to irreversibly move throughthe needle sheath aperture 4770 of the safety lock 4700 in a distaldirection. Said another way, the angled ridge 4725 can be configured insuch a way as to allow the proximal end portion 4722 of the needlesheath 4720 to move through the needle sheath aperture 4770 in a distaldirection, but not in a proximal direction. The needle sheath aperture4770 has retaining tabs 4771 configured to engage the proximal end ofthe angled ridge 4725 when the needle sheath 4720 is moved in a proximaldirection. In this manner, the retaining tabs 4771 prevent the proximalmovement of the needle sheath with respect to the safety lock 4700.Further, the retaining tabs 4771 are configured to engage the proximalend of the angled ridge 4725 when the safety lock 4700 is moved in adistal direction. Said another way, as shown in FIG. 33, the needlesheath 4720 is removed from the needle 4452 when the safety lock 4700 ismoved in a distal direction with respect to the housing 4110.

FIGS. 35 and 36 show the base 4302 of the medical injector 4000. Thebase 4302 includes a proximal surface 4310, a distal surface 4330 andbase connection knobs 4358. The base 4302 defines a needle aperture4350, a safety lock protrusion aperture 4352, a battery isolationprotrusion aperture 4354, a safety lock actuator opening 4356, and pulltab openings 4360. The needle aperture 4350 is configured to receive theneedle 4452 when the medical injector 4000 is actuated. The safety lockprotrusion aperture 4352 of the base 4302 receives the safety lockprotrusion 4742 of the safety lock 4700. The battery isolationprotrusion aperture 4354 of the base 4302 receives the battery isolationprotrusion 4235 of the cover 4200 and the stopper 4743 of the safetylock 4700. The safety lock actuator opening 4356 receives the safetylock actuator 4744 of the safety lock 4700. The pull tab openings 4360are configured to receive the pull tabs 4741 of the safety lock 4700.

The proximal surface 4310 of the base 4302 includes an actuator 4311,guide members 4312, and protrusions 4313. The actuator 4311 is anelongate member configured to engage the substrate 4924 of theelectronic circuit system 4900. As described above, the opening 4945 ofthe second actuation portion 4946 is configured to receive the actuator4311 of the base 4302. The guide members 4312 of the base 4302 areconfigured to engage and/or slide within the base rail grooves 4127 ofthe housing 4110, as described above. The protrusions 4313 of the base4302 are configured to engage the tapered surfaces 4349 of theextensions 4343 of the release member 4340. As described in furtherdetail herein, when the safety lock 4700 is removed and the base 4302 ismoved in a proximal direction with respect to the housing 4110, theprotrusion 4313 of the base 4302 are configured to move the extensions4343 of the release member 4340 closer to each other, actuating themedicament delivery mechanism 4500. As described above, the baseconnection knobs 4358 are configured to engage the base retentionrecesses 4125A, 4125B in a way that allows proximal movement of the base4302 but limits distal movement of the base 4302.

As shown in FIG. 37, the medical injector 4000 is first enabled bymoving the medicament delivery device 4000 from a first configuration toa second configuration by moving the cover 4200 from a first position toa second position. The cover 4200 is moved from the first position tothe second position by moving it with respect to the housing 4110 in thedirection shown by the arrow EE in FIG. 37. When the cover 4200 is movedwith respect to the housing 4110 in the direction EE, the batteryisolation protrusion 4235 is removed from the area between the batteryclip 4910 and the second surface 4966 of the battery assembly 4962. Inthis manner, the battery assembly 4962 can be operatively coupled to theelectronic circuit system 4900 when the cover 4200 is removed, therebyproviding power to the electronic circuit system 4900. Similarly stated,this arrangement allows the electronic circuit system 4900 to beactuated when the cover 4200 is removed.

When power is provided, as described above, the electronic circuitsystem 4900 can output one or more predetermined electronic outputs. Forexample, in some embodiments, the electronic circuit system 4900 canoutput an electronic signal associated with recorded speech to theaudible output device 4956. Such an electronic signal can be, forexample, associated with a .WAV file that contains a recordedinstruction instructing the user in the operation of the medicalinjector 4000. Such an instruction can state, for example, “remove thesafety tab near the base of the auto-injector.” The electronic circuitsystem 4900 can simultaneously output an electronic signal to one and/orboth of the LEDs 4958A, 4958B thereby causing one and/or both of theLEDs 4958A, 4958B to flash a particular color. In this manner, theelectronic circuit system 4900 can provide both audible and visualinstructions to assist the user in the initial operation of the medicalinjector 4000.

In other embodiments, the electronic circuit system 4900 can output anelectronic output associated with a description and/or status of themedical injector 4000 and/or the naloxone composition 4420 containedtherein. For example, in some embodiments, the electronic circuit system4900 can output an audible message indicating the symptoms for which thenaloxone composition should be administered, the expiration date of thenaloxone composition, the dosage of the naloxone composition or thelike.

As described above, the medical injector 4000 can be can be repeatedlymoved between the first configuration and the second configuration whenthe cover 4200 is moved repeatedly between the first position and thesecond position respectively. Said another way, the cover 4200 can beremoved and replaced about the housing 4110 any number of times. Whenthe cover 4200 is moved from the second position to the first position,the battery isolation protrusion 4235 is inserted between the batteryclip 4910 and the second surface 4966 of the battery assembly 4962,deactivating the electronic circuit system 4900. When the cover is movedfrom the first position to the second position a second time, theelectronic circuit system 4900 is once again activated. In this manner,the cover 4200 can be removed and the electronic circuit system 4900 canoutput an electronic output without compromising the sterility of theneedle 4452.

After the cover 4200 is removed from the housing 4110, the medicalinjector 4000 can be moved from the second configuration to a thirdconfiguration by moving the safety lock 4700 from a first position to asecond position. The safety lock 4700 is moved from a first position toa second position by moving the safety lock 4700 with respect to thehousing 4110 in the direction shown by the arrow FF in FIG. 38. When thesafety lock 4700 is moved from the first position to the secondposition, the safety lock protrusion 4742 is removed from between theextensions 4343 of the release member 4340, thereby enabling themedicament delivery member 4500. Moreover, as shown in FIGS. 26 and 27,when the safety lock 4700 is moved from the housing 4110, the actuator4744 of the safety lock 4700 moves in the direction CC as shown in FIG.27, irreversibly moving the first switch 4972 from a first state (e.g.,a state of electrical continuity) to a second state (e.g., a state ofelectrical discontinuity). When the actuator 4744 of the safety lock4700 moves irreversibly the first switch 4972 of the electronic circuitsystem 4900 to the second state, the electronic circuit system 4900 canoutput one or more predetermined electronic outputs. For example, insome embodiments, a processor (not shown) can output an electronicsignal associated with recorded speech to the audible output device4956. Such an electronic signal can be, for example, associated with arecorded message notifying the user of the status of the medicalinjector 4000. Such a status message can state, for example, “If readyto use the naloxone medical injector, pull off the red safety guard.”The electronic circuit system 4900 can also simultaneously output anelectronic signal to one and/or both of the LEDs 4958A, 4958B, therebycausing one and/or both of the LEDs 4958A, 4958B to stop flashing,change color or the like.

In some embodiments, the first actuation portion 4926 and the actuator4744 can be configured such that the actuator 4744 must move apredetermined distance before the actuator 4744 engages the boundary4929 of the opening 4928. For example, in some embodiments, the actuator4744 must move approximately 0.200 inches before the actuator 4744engages the boundary 4929 of the opening 4928. In this manner, thesafety lock 4700 can be moved slightly without irreversibly moving thefirst switch 4972 of the electronic circuit system 4900 to the secondstate. Accordingly, this arrangement will permit the user toinadvertently and/or accidentally move the safety lock 4700 withoutactuating the electronic circuit system 4900.

In some embodiments, the electronic circuit system 4900 can beconfigured to output the status message for a predetermined time period,such as, for example, five seconds. After the predetermined time periodhas elapsed, the electronic circuit system 4900 can output an audiblemessage further instructing the user in the operation of the medicalinjector 4000. Such an instruction can state, for example, “Place thebase of the auto-injector against the patient's thigh. To complete theinjection, press the base firmly against the patient's thigh.” In someembodiments, the electronic circuit system 4900 can simultaneouslyoutput an electronic signal to one and/or both of the LEDs 4958A, 4958B,thereby causing one and/or both of the LEDs 4958A, 4958B to flash aparticular color. In this manner, the electronic circuit system 4900 canprovide both audible and/or visual instructions to assist the user inthe placement and actuation of the medical injector 4000. In someembodiments, the electronic circuit system 4900 can be configured torepeat the instructions after a predetermined time period has elapsed.

As described above, in other embodiments, the medical injector 4000 canhave a network interface device (not shown) configured to operativelyconnect the electronic circuit system 4900 to a remote device (notshown) and/or a communications network (not shown). In this manner, theelectronic circuit system 4900 can send a wireless signal notifying aremote device that the safety lock 4700 of the medical injector 4000 hasbeen removed and that the medical injector 4000 has been armed. In otherembodiments, the electronic circuit system 4900 can send a wirelesssignal (e.g., a wireless 911 call) notifying an emergency responder thatthe medical injector 4000 has been armed.

After the safety lock 4700 is moved from the first position to thesecond position, the medical injector 4000 can be moved from the thirdconfiguration to a fourth configuration by moving the base 4302 from afirst position to a second position. Similarly stated, the medicalinjector 4000 can be actuated by the system actuator assembly 4300 bymoving the base 4302 distally relative to the housing 4110. The base4302 is moved from its first position to its second position by placingthe medical injector 4000 against the body of the patient and moving thebase 4302 with respect to the housing 4110 in the direction shown by thearrow GG in FIG. 39. Moving the base 4302 from the first position to thesecond position causes the protrusions 4313 on the proximal surface 4310of the base 4302 to engage the tapered surfaces 4349 of the extensions4343 of the release member 4340, thereby moving the extensions 4313together. The inward movement of the extensions 4343 causes the releasemember 4340 to become disengaged from the distal end portion of thehousing 4110, thereby allowing the release member 4340 to be movedproximally along its longitudinal axis as the spring 4370 expands.

When the base 4302 is moved from the first position to the secondposition, the system actuator 4300 actuates the medicament deliverymechanism 4500, thereby placing the medical injector 4500 in its fourthconfiguration (i.e., the needle insertion configuration), as shown inFIGS. 39 and 40. More particularly, when the medical injector is in itsfourth configuration, the puncturer 4341 of the release member 4340 isin contact with and/or disposed through the frangible seal 4573 of thegas container 4570.

After the frangible seal 4573 has been punctured, an actuating portionof a compressed gas can escape from the gas container 4570 and flow viathe gas passageway 4144 into the medicament cavity 4157. The gas appliesgas pressure to the movable member 4530 causing the movable member 4530and the carrier 4520 to move in a distal direction within the medicamentcavity 4157, as shown by the arrow HH in FIG. 40. When the carrier 4520moves distally within the medicament cavity 4157, the carrier 4520 andthe medicament container 4400 are in a first configuration. Accordingly,as described above, the medicament container 4400 is connected to thecarrier 4520 by a “snap fit” connection. In this manner, the medicamentcontainer 4400 and the needle 4452 contemporaneously move with movablemember 4530 and/or the carrier 4520 in a distal direction. As describedabove, the proximal end portion 4456 of the needle 4452 is connected tothe distal end portion 4522 of the carrier 4520 and is spaced from theseal 4406 of the medicament container 4400 when the carrier 4520 is inits first configuration. Said another way, the medicament container 4400and the needle 4452 do not define a medicament delivery path when thecarrier 4520 is in the first configuration. The movement of the needle4452 in a distal direction causes the distal end portion of the needle4452 to exit the housing 4110 and enter the body of a patient prior toadministering the naloxone composition 4420.

After the carrier 4520 and/or the needle 4452 have moved within themedicament cavity 4157 a predetermined distance, the carrier 4520 andthe medicament container 4400 are moved from the first configuration toa second configuration. In the second configuration of the carrier 4520,the medicament container 4400 is released from the “snap-fit” allowingthe medicament container 4400 and the movable member 4530 to continue tomove in a distal direction relative to the carrier 4520. Said anotherway, the medicament container 4400 is configured to slidably move withinthe carrier 4520 when the carrier is moved from the first configurationto the second configuration. As the medicament container 4400 continuesto move within the carrier 4520, the proximal end portion 4456 of theneedle 4452 contacts and punctures the seal 4406 of the medicamentcontainer 4400. This allows the medicament contained in the medicamentcontainer 4400 to flow into the lumen (not shown) defined by the needle4452, thereby defining a medicament delivery path.

After the medicament container 4400 contacts the distal end of thecarrier 4520, the medicament container 4400 stops moving within thecarrier 4520 while the movable member 4530 continues to move in a distaldirection, as shown by the arrow II in FIG. 41. This causes the pistonportion 4534 of the movable member 4530 to move within the medicamentcontainer 4400 containing the naloxone composition 4420. As the pistonportion 4534 of the movable member 4530 moves within the medicamentcontainer 4400, the piston portion 4534 contacts the elastomeric member4410 and generates a pressure upon the naloxone composition 4420contained within the medicament container 4400, thereby allowing atleast a portion of the naloxone composition 4420 to flow out of themedicament container 4400 and into the lumen defined by the needle 4452.The medicament is delivered to a body of a user via the medicamentdelivery path defined by the medicament container 4400 and the needle4452.

As shown in FIG. 42, after the movable member 4530 moves a predetermineddistance within the medicament container 4400, the gas valve actuator4527 of the carrier 4520 engages the gas relief valve (not shown in FIG.42) of the movable member 4530 thereby allowing the pressurized gascontained within the gas chamber (i.e., the volume within the medicamentcavity 4157 between the proximal end of the housing 4110 and theproximal end of the movable member 5530) to escape. Similarly stated,the gas valve actuator 4527 of the carrier 4520 engages the gas reliefvalve of the movable member 4530, the pressure within the housing 4110is reduced, thereby ending the injection event. In this manner, thepre-injection distance between the proximal end portion of the movablemember 4530 and the gas valve actuator 4527 of the carrier 4520 can beadjusted to control the amount of the naloxone composition 4420 to beinjected. After the gas pressure within the medicament cavity 4157decreases below a certain level, the force exerted by the retractionspring 4590 on the carrier 4520 can be sufficient to cause the carrier4520 to move proximally within the housing 4110 (i.e., to retract), asshown by the arrow JJ in FIG. 42.

As described above, the actuator 4311 of the base 4302 actuates theelectronic circuit 4900 to trigger a predetermined output or sequence ofoutputs when the base 4302 is moved from its first position to itssecond position (see, e.g., FIGS. 24-28). When the actuator 4311 ismoved in a proximal direction relative to the opening 4945, as shown bythe arrow DD in FIG. 28, the electronic circuit system 4900 is actuatedto output one or more predetermined electronic outputs. For example, insome embodiments, the electronic circuit system 4900 can output anelectronic signal associated with recorded speech to the audible outputdevice 4956. Such an electronic signal can be, for example, associatedwith an audible countdown timer, instructing the user on the duration ofthe injection procedure. Said another way, if it takes, for example, tenseconds to complete an injection, an audible countdown timer can countfrom ten to zero ensuring that the user maintains the medical injector4000 in place for the full ten seconds. In other embodiments, theelectronic signal can be, for example, associated with a recordedmessage notifying the user that the injection is complete, instructingthe user on post-injection disposal and safety procedures, instructingthe user on post-injection medical treatment or the like. Such a statusmessage can state, for example, “The injection is now complete. Pleaseseek further medical attention from a doctor.” The electronic circuitsystem 4900 can also simultaneously output an electronic signal to oneand/or both LEDs 4958A, 4958B, thereby causing one and/or both LEDs4958A, 4958B to stop flashing, change color or the like, to provide avisual indication that the injection is complete. In other embodiments,the electronic circuit system 4900 can send a wireless signal notifyinga remote device that the injection is complete. In this manner, apatient's compliance can be monitored.

In some embodiments, the second actuation portion 4946 and the actuator4311 can be configured such that the base 4500 and/or the actuator 4311must move a predetermined distance before the actuator 4311 engages theboundary 4949 of the opening 4945. For example, in some embodiments, theactuator 4311 must move approximately 0.200 inches before the actuator4311 engages the boundary 4949 of the opening 4945. In this manner, thebase 4700 can be moved slightly without irreversibly moving the secondswitch 4973 of the electronic circuit system 4900 to the second state.Accordingly, this arrangement will permit the user to inadvertentlyand/or accidentally move the base 4500 without actuating the electroniccircuit system 4900.

Although the electronic circuit system 4900 is shown and described aboveas having two irreversible switches (e.g., switch 4972 and switch 4973),in other embodiments, an electronic circuit system can have any numberof switches. Moreover, such switches can be either reversible orirreversible. For example, FIGS. 43-48 show portions of a medicamentdelivery device 5000 having an electronic circuit system 5900 havingthree irreversible switches.

The medicament delivery device 5000 is similar to the medical injector4000 described above. As shown in FIGS. 43 and 44 (which show onlyportions of the medicament delivery device 5000), the medicamentdelivery device 5000 includes a housing 5110, a delivery mechanism (notshown), an electronic circuit system 5900, a cover (not shown), a safetylock (not shown, similar to safety lock 4700) and a base (not shown,similar to base 4302). The structure and operation of the deliverymechanism, the cover, the safety lock and the base are similar to thestructure and operation of the delivery mechanism 4500, the cover 4200,the safety lock 4700 and the base 4302, respectively. Accordingly, onlythe electronic circuit system 5900 and the housing 5110 are described indetail below.

As shown in FIG. 43, the housing 5110 has a proximal end portion 5140and a distal end portion 5120. The housing 5110 defines a gas cavity(not shown), a medicament cavity (not shown) and an electronic circuitsystem cavity 5153. The gas cavity and medicament cavity of the housing5110 of the medicament delivery device 5000 are similar to the gascavity 4154 and the medicament cavity 4157, shown and described abovewith reference to FIGS. 10 and 11.

The electronic circuit system cavity 5153 is configured to receive theelectronic circuit system 5900. As described above, the electroniccircuit system cavity 5153 is fluidically and/or physically isolatedfrom the gas cavity and/or the medicament cavity by a sidewall 5148. Thehousing 5110 has protrusions 5149 configured to stabilize the electroniccircuit system 5900 when the electronic circuit system 5900 is disposedwithin the electronic circuit system cavity 5153. The housing 5110 alsodefines connection apertures (not shown) configured to receiveconnection protrusions 5171 of the electronic circuit system 5900 (seee.g., FIG. 44). In this manner, the electronic circuit system 5900 canbe coupled to the housing 5110 within the electronic circuit systemcavity 5153 (see e.g., FIG. 47). In other embodiments, the electroniccircuit system 5900 can be coupled within the electronic circuit systemcavity 5153 by any other suitable means, such as an adhesive, a clipand/or the like.

The housing 5110 includes an actuation protrusion 5114 disposed withinthe electronic circuit system cavity 5153. As described in more detailherein, an angled end portion 5115 of the actuation protrusion 5114 ofthe housing 5110 is configured to engage a third actuation portion 5976of a substrate 5924 of the electronic circuit system 5900 when theelectronic circuit system 5900 is coupled to the housing 5110.

As shown in FIG. 47, the electronic circuit system 5900 is configured tofit within the electronic circuit system cavity 5153 of the housing5110. Accordingly, as described above, the electronic circuit system5900 is physically and/or fluidically isolated from the medicamentcavity, the gas cavity and/or the medicament delivery path within themedicament delivery device 5000 (not shown). As described herein, theelectronic circuit system 5900 is configured to output an electronicoutput associated with a use of the medicament delivery device 5000.

As shown in FIG. 44, the electronic circuit system 5900 is similar tothe electronic circuit system 4900 described above. The electroniccircuit system 5900 of the medicament delivery device 5000 includes anelectronic circuit system housing 5170, a printed circuit board 5922, abattery assembly 5962, an audio output device 5956, two light emittingdiodes (LEDs) 5958A, 5958B and a battery clip 5910. The electroniccircuit system housing 5170, the battery assembly 5962, the audio outputdevice 5956, the two light emitting diodes (LEDs) 5958A, 5958B and thebattery clip 5910 are similar to the electronic circuit system housing4170, the battery assembly 4962, the audio output device 4956, the twolight emitting diodes (LEDs) 4958A, 4958B and the battery clip 4910 ofthe electronic circuit system 4900 described above. Thus, a detaileddiscussion of these components is omitted.

The electronic circuit system 5900 also includes a processor 5950configured to process electronic inputs (e.g., from input switches) andproduce electronic outputs. As described herein, such electronic outputscan include audio or visual outputs associated with a use of themedicament delivery device 5000. The processor 5950 can be acommercially-available processing device dedicated to performing one ormore specific tasks. For example, in some embodiments, the processor5950 can be a commercially-available microprocessor, such as the SonixSNC 12060 or the SNC 26120 voice synthesizers. Alternatively, theprocessor 5950 can be an application-specific integrated circuit (ASIC)or a combination of ASICs, which are designed to perform one or morespecific functions. In yet other embodiments, the processor 5950 can bean analog or digital circuit, or a combination of multiple circuits.

The processor 5950 can include a memory device (not shown) configured toreceive and store information, such as a series of instructions,processor-readable code, a digitized signal, or the like. The memorydevice can include one or more types of memory. For example, the memorydevice can include a read only memory (ROM) component and a randomaccess memory (RAM) component. The memory device can also include othertypes of memory suitable for storing data in a form retrievable by theprocessor 5950, for example, electronically-programmable read onlymemory (EPROM), erasable electronically-programmable read only memory(EEPROM), or flash memory.

FIG. 45 shows the printed circuit board 5922 of the electronic circuitsystem 5900. FIG. 46 is a schematic illustration of the electroniccircuit system 5900. The printed circuit board 5922 of the electroniccircuit system 5900 includes a substrate 5924, a first actuation portion5926 (including a first switch 5972), a second actuation portion 5946(including a second switch 5973), and a third actuation portion 5976(including an electronic circuit system configuration switch 5974). Thesubstrate 5924 of the printed circuit board 5922 includes the electricalcomponents necessary for the electronic circuit system 5900 to operateas desired. For example, the electrical components can includeresistors, capacitors, inductors, switches, microcontrollers,microprocessors and/or the like.

The first actuation portion 5926 and the second actuation portion 5946are similar to the first actuation portion 4926 and the second actuationportion 4946 of the electronic circuit system 4900, described above (seee.g., FIG. 44), and are therefore not described or labeled in detail.The third actuation portion 5976 includes a third electrical conductor5936 (see e.g., FIG. 45) and defines an actuation aperture 5975 having aboundary 5979, and a tear propagation limit aperture 5978. As shown inFIGS. 44 and 48, the actuation aperture 5975 of the third actuationportion 5976 is configured to receive the angled end portion 5115 of theactuation protrusion 5114 of the housing 5110 when the electroniccircuit system 5900 is disposed within the electronic circuit systemcavity 5153. The boundary 5979 of the actuation aperture 5975 has adiscontinuous shape, such as, for example, a teardrop shape, thatincludes a stress concentration riser 5977. The discontinuity and/or thestress concentration riser 5977 of the boundary 5979 can be of anysuitable shape to cause the substrate 5924 to deform in a predetermineddirection when the angled end portion 5115 of the actuation protrusion5114 of the housing 5110 is inserted into the actuation aperture 5975(see e.g., FIG. 48), as described below.

The third electrical conductor 5936 includes the electronic circuitsystem configuration switch 5974 (see e.g., FIG. 45) disposed betweenthe actuation aperture 5975 and the tear propagation limit aperture5978, which can be, for example, a frangible portion of the thirdelectrical conductor 5436. As shown in FIGS. 47 and 48, when theelectronic circuit system 5900 is attached to the housing 5110, aportion of the angled portion 5115 of the actuation protrusion 5114 isdisposed within the actuation aperture 5975 of the third actuationportion 5976, as shown by the arrow KK in FIG. 48. Continued movement ofthe angled portion 5115 of the actuation protrusion 5114 within thethird actuation portion 5976 of the substrate 5924 causes the thirdactuation portion 5976 of the substrate 5924 to tear, thereby separatingthe portion of the third electrical conductor 5936 including theelectronic circuit system configuration switch 5974. Said another way,when the electronic circuit system 5900 is attached to the housing 5110,the actuation protrusion 5114 moves irreversibly the electronic circuitsystem configuration switch 5974 from a first state (e.g., a state ofelectrical continuity) to a second state (e.g., a state of electricaldiscontinuity).

The tear propagation limit aperture 5978 is configured to limit thepropagation of the tear in the substrate 5924. Said another way, thetear propagation limit aperture 5978 is configured to ensure that thetear in the substrate 5924 does not extend beyond the tear propagationlimit aperture 5978. The tear propagation limit aperture 5978 can be anyshape configured to limit the propagation of a tear and/or disruption ofthe substrate 5924. For example, the tear propagation limit aperture5978 can be oval shaped. In other embodiments, the boundary of the tearpropagation limit aperture 5978 can be reinforced to ensure that thetear in the substrate 5924 does not extend beyond the tear propagationlimit aperture 5978. The angled end portion 5115 of the actuationprotrusion 5114 ensures that the tear in the substrate 5924 propagatesin the desired direction. Said another way, the angled end portion 5115of the actuation protrusion 5114 ensures that the tear in the substrate5924 occurs between the actuation aperture 5975 and the tear propagationlimit aperture 5978.

When the actuation protrusion 5114 of the housing 5110 movesirreversibly the electronic circuit system configuration switch 5974 ofthe electronic circuit system 5900 from the first state to the secondstate, the electronic circuit system 5900 can be moved between a firstconfiguration and a second configuration. For example, in someembodiments, irreversibly moving the electronic circuit systemconfiguration switch 5974 of the electronic circuit system 5900 to thesecond state places the electronic circuit system 5900 in the secondconfiguration such that when power is applied to the electronic circuitsystem 5900, the electronic circuit system 5900 recognizes that themedicament delivery device 5000 is a certain type of medicament deliverydevice and/or is in a certain configuration. In some embodiments, thehousing can be devoid of the actuation protrusion 5114, thus theelectronic circuit system configuration switch 5974 is maintained in itsfirst state when the electronic circuit system 5900 is attached to thehousing 5110. In this manner, the electronic circuit systemconfiguration switch 5974 can enable the electronic circuit system 5900to be used in different types and/or configurations of medicamentdelivery devices. The dual functionality of the electronic circuitsystem 5900 enables production of the same electronic circuit system5900 for multiple devices, thereby permitting mass production anddecreasing the cost of production of the electronic circuit system 5900.

For example, in some embodiments the electronic circuit system 5900 canbe used in either an actual medicament delivery device or a simulatedmedicament delivery device. A simulated medicament delivery device can,for example, correspond to an actual medicament delivery device and canbe used, for example, to train a user in the operation of thecorresponding actual medicament delivery device.

The simulated medicament delivery device can simulate the actualmedicament delivery device in any number of ways. For example, in someembodiments, the simulated medicament delivery device can have a shapecorresponding to a shape of the actual medicament delivery device, asize corresponding to a size of the actual medicament delivery deviceand/or a weight corresponding to a weight of the actual medicamentdelivery device. Moreover, in some embodiments, the simulated medicamentdelivery device can include components that correspond to the componentsof the actual medicament delivery device. In this manner, the simulatedmedicament delivery device can simulate the look, feel and sounds of theactual medicament delivery device. For example, in some embodiments, thesimulated medicament delivery device can include external components(e.g., a housing, a needle guard, a sterile cover, a safety lock or thelike) that correspond to external components of the actual medicamentdelivery device. In some embodiments, the simulated medicament deliverydevice can include internal components (e.g., an actuation mechanism, acompressed gas source, a medicament container or the like) thatcorrespond to internal components of the actual medicament deliverydevice.

In some embodiments, however, the simulated medicament delivery devicecan be devoid of a medicament and/or those components that cause themedicament to be delivered (e.g., a needle, a nozzle or the like). Inthis manner, the simulated medicament delivery device can be used totrain a user in the use of the actual medicament delivery device withoutexposing the user to a needle and/or a medicament. Moreover, thesimulated medicament delivery device can have features to identify it asa training device to prevent a user from mistakenly believing that thesimulated medicament delivery device can be used to deliver amedicament. For example, in some embodiments, the simulated medicamentdelivery device can be of a different color than a corresponding actualmedicament delivery device. Similarly, in some embodiments, thesimulated medicament delivery device can include a label clearlyidentifying it as a training device.

The actuation of the medicament delivery device configuration switch5974 can configure the electronic circuit system 5900 to output adifferent electronic output when the medicament delivery device 5000 isa simulated medical injector than when the medicament delivery device5000 is an actual medical injector. Said yet another way, the electroniccircuit system 5900 can be configured to output a first series ofelectronic outputs when the electronic circuit system configurationswitch 5974 is in the first state and a second series of electronicoutputs when the electronic circuit system configuration switch 5974 isin the second state. In this manner, the electronic circuit systemconfiguration switch 5974 can enable the same electronic circuit system5900 to be used in both simulated medicament delivery devices and actualmedicament delivery devices. When used on an actual medicament deliverydevice, for example, the housing can be devoid of the actuationprotrusion 5114. The dual functionality of the electronic circuit system5900 can decrease the cost of production of the electronic circuitsystem 5900 of the medicament delivery device 5000.

In other embodiments, moving the electronic circuit system configurationswitch 5974 to the second state can place the electronic circuit system5900 in any number of different functional configurations. For example,moving the electronic circuit system configuration switch 5974 from thefirst state to the second state can indicate the type of medicament inthe medicament container, the dosage of the medicament and/or thelanguage of the audible electronic outputs output by the electroniccircuit system 5900.

In still other embodiments, any number of electronic circuit systemconfiguration switches can be used. For example, multiple switches canbe used to configure the electronic circuit system 5900 to output usageinstructions in any number of languages. For example, if an electroniccircuit system contained three configuration switches (e.g., switches A,B and C), switch A can correspond to English instructions, switch B toSpanish instructions and switch C to German instructions. Further,moving both switch A and B to the second state might correspond toFrench instructions. In this manner, a single electronic circuit system5900 can be configured to output instructions in multiple languages.

The needle 4452, as well as any other needles shown and describedherein, can have any diameter and/or length to facilitate the injectionof the naloxone composition 4420. For example, the needle can have alength suitable to penetrate clothing and deliver the naloxone via asubcutaneous injection and/or an intramuscular injection. In someembodiments, the needle 4452 (and any needle disclosed herein) can havea length of greater than 1 inch, greater than 1.5 inches, greater than 2inches, greater than 2.5 inches or greater than 3 inches. In someembodiments, the needle 4452 (and any needle disclosed herein) can havea lumen diameter of approximately between 19 gauge and 31 gauge.

Although the medical injectors 4000 and 5000 are shown and describedabove as being auto-injectors configured to deliver the naloxonecompositions described herein via injection through a needle (e.g.,needle 4452), in other embodiments, a medicament delivery device can beconfigured to deliver the naloxone compositions described herein via anysuitable delivery member, and in any suitable manner. For example, insome embodiments, a medicament delivery device can include a deliverymember that delivers the naloxone composition into the body viainhalation and/or intranasal delivery.

For example, FIG. 49 is a schematic illustration of a medicamentdelivery device 6000 according to an embodiment that is configured todeliver a naloxone composition intranasally and/or via inhalation. Themedicament delivery device 6000 includes a housing 6110, a medicamentcontainer 6400, a delivery member 6450 and an energy storage member6570. The medicament container 6400 is at least partially disposedwithin the housing 6110, and contains (i.e., is filled or partiallyfilled with) a naloxone composition 6420. The delivery member 6450 iscoupled to the medicament container 6400, and, as described herein, isconfigured to delivery the naloxone composition from the medicamentcontainer 6400 intranasally and/or via inhalation. The energy storagemember 6570 is disposed within the housing 6110, and is configured toproduce a force F4 to deliver the naloxone composition 6420 (e.g., fromthe medicament container 6400 to a body).

The naloxone composition 6420 can be any of the naloxone compositionsdescribed herein. In particular, the naloxone composition 6420 caninclude an effective amount of naloxone or salts thereof, atonicity-adjusting agent, and a pH adjusting agent. The naloxonecomposition 6420 can be formulated such that the osmolality of thenaloxone composition 6420 ranges from about 250-350 mOsm and the pHranges from about 3-5.

In some embodiments, the naloxone composition 6420 can include anysuitable concentration of 4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)morphinan-6-one. In some embodiments, for example, the naloxonecomposition 6420 has a concentration of4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)morphinan-6-one betweenapproximately 0.01 mg/mL and approximately 60 mg/mL. In otherembodiments, the naloxone composition 6420 has a concentration of4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)morphinan-6-one betweenapproximately 0.05 mg/mL and approximately 2 mg/mL.

The tonicity-adjusting agent can be any of the tonicity-adjusting agentsdescribed herein, and can be included within the naloxone composition6420 in any suitable amount and/or concentration. For example, in someembodiments, the tonicity-adjusting agent includes at least one ofdextrose, glycerin, mannitol, potassium chloride or sodium chloride. Inother embodiments, the tonicity-adjusting agent includes sodium chloridein an amount such that a concentration of sodium chloride is betweenapproximately 0.1 mg/mL and approximately 20 mg/mL.

The pH adjusting agent can be any of the pH adjusting agents describedherein, and can be included within the naloxone composition 6420 in anysuitable amount and/or concentration. For example, in some embodiments,the pH adjusting agent includes at least one of hydrochloric acid,citric acid, citrate salts, acetic acid, acetate salts, phosphoric acidor phosphate salts. In other embodiments, the pH adjusting agentincludes a dilute hydrochloric acid.

The medicament container 6400 can be any container suitable for storingthe naloxone composition 6420. In some embodiments, the medicamentcontainer 6400 can be, for example, a pre-filled syringe, a pre-filledcartridge, a vial, an ampule or the like. In other embodiments, themedicament container 6400 can be a container having a flexible wall,such as, for example, a bladder. Although shown and described as beingpartially disposed within the housing 6110, in other embodiments, themedicament container 6400 can be disposed entirely within the housing6110. Moreover, in some embodiments, the medicament container 6400 canbe movably disposed within the housing 6110, such as, for example, in amanner similar to the medicament container 4400 shown and describedabove.

The delivery member 6450 is coupled to the medicament container 6400 anddefines, at least in part, a flow path through which the naloxonecomposition 6420 can be delivered into a body. Although shown as beingdirectly coupled to a distal end portion of the medicament container6400, in other embodiments, the delivery member 6450 can be indirectlycoupled to the medicament container 6400, (e.g., via the housing 6110).

Moreover, in some embodiments, the delivery member 6450 can be coupledto, but fluidically isolated from, the medicament container 6400 priorto actuation of the energy storage member 6570. In this manner, themedicament delivery device 6000 can be stored for extended periods oftime while maintaining the sterility of the naloxone composition 6420contained within the medicament container 6400, reducing (oreliminating) any leakage of the naloxone composition 6420 from themedicament container 6400 or the like. This arrangement also reducesand/or eliminates the assembly operations (e.g., the operation ofcoupling the delivery member 6450 to the medicament container 6400)before the medicament delivery device 6000 can be used to administer thenaloxone composition 6200. In this manner, the medicament deliverydevice 6000 produces a quick and accurate mechanism for delivering thenaloxone composition 6420. Similarly stated by reducing and/oreliminating the assembly operations prior to use, this arrangementreduces likelihood that performance of medicament delivery device 6000and/or the delivery member 6450 will be compromised (e.g., by animproper coupling, a leak or the like).

In some embodiments, the delivery member 6450 can be coupled to themedicament container 6400 via a coupling member (not shown in FIG. 49)having similar functionality to the carrier 4520 shown and describedabove with respect to the medicament delivery device 4000. In such anembodiment, the medicament container 6400 and/or the delivery member6450 can be configured to move relative to the coupling member when theenergy storage member 6570 is actuated. Such movement can fluidicallycouple the delivery member 6450 and the medicament container 6400,thereby defining a flow path through which the naloxone composition 6420can be delivered to the patient.

In some embodiments, the delivery member 6450 can enhance the deliveryof the naloxone composition 6420 thereby improving the efficacy of thenaloxone composition 6420. Similarly stated, in some embodiments, thedelivery member 6450 can produce a flow of the naloxone composition 6420having desired characteristics to enhance the absorption rate of thenaloxone composition 6420, to minimize the delivery of the naloxonecomposition 6420 to regions of the body in which such delivery is lesseffective (e.g., the throat, etc.) or the like.

For example, in some embodiments, the delivery member 6450 can produce acontrolled flow rate of the naloxone composition 6420. In suchembodiments, the delivery member 6450 can include one or more floworifices, a tortuous flow path or the like, to produce a desiredpressure drop and/or to control the flow through the delivery member6450. For example, in some embodiments, the delivery member 6450 can beconfigured to minimize excessive delivery of the naloxone composition6420. For example, for intranasal applications, the delivery member 6450can reduce the likelihood of excess deposition of the naloxonecomposition 6420 on the mucosal membrane, which can result in a portionof the naloxone composition 6420 being nonabsorbed (e.g., running out ofthe nose or into the throat).

In some embodiments, the delivery member 6450 can be configured toatomize the naloxone composition 6420 to produce a spray for intransaladministration. For example, in some embodiments, the delivery member6450 can produce an atomized spray of the naloxone composition having adesired spray geometry (e.g., spray angle and/or plume penetration)and/or droplet size distribution. In some embodiments, for example, thedelivery member 6450 can include two chambers to allow substantiallysimultaneous deliver o the naloxone composition 6420 into both nostrilsof a patient. Moreover, the delivery member 6450 can be cooperativelyconfigured with the energy storage member 6570 to produce an atomizedspray of the naloxone composition having a desired spray geometry and/ordroplet size distribution. In this manner, the medicament deliverydevice 6000 can produce a consistent spray to enhance the efficacy ofthe naloxone composition 6420 under a wide variety of conditions.

In some embodiments, for example, the delivery member 6450 and theenergy storage member 6570 can be cooperatively configured such that,when the energy storage member 6570 is actuated, the medicament deliverydevice 6000 produces an atomized spray of the naloxone composition 6420having a substantial portion of the droplets therein having sizedistribution of between about 10 microns and about 20 microns. In thismanner, the amount of the naloxone composition 6420 delivered to thelungs (e.g., the amount of smaller droplets that bypass the mucosalmembrane) and/or the amount of the naloxone composition 6420 that runsinto the throat (e.g., the amount of larger droplets) is minimized. Insome embodiments, the delivery member 6450 and the energy storage member6570 are cooperatively configured to produce a spray of the naloxonecomposition 6420 having a droplet size distribution whereinapproximately 85 percent of the droplets have a size of betweenapproximately 10 microns and 150 microns.

As described above, in some embodiments, the energy storage member 6570is configured to “match” the delivery member 6450. Said another way, insome embodiments, the energy storage member 6570 is configured toproduce the force F4 within a predetermined range to ensure the desiredfunctionality of the delivery member 6450. Accordingly, the energystorage member 6570 can be any suitable device or mechanism that, whenactuated, produces the desired force F4 to deliver the naloxonecomposition 6420 as described herein. By employing the energy storagemember 6570 to produce the force F4, rather than relying on a user tomanually produce the delivery force, the naloxone composition 6420 canbe delivered into the body at the desired pressure and/or flow rate, andwith the desired characteristics, as described above. Moreover, thisarrangement reduces the likelihood of partial delivery (e.g., that mayresult if the user is interrupted or otherwise rendered unable tocomplete the delivery).

In some embodiments, the energy storage member 6570 can be a mechanicalenergy storage member, such as a spring, a device containing compressedgas, a device containing a vapor pressure-based propellant or the like.In other embodiments, the energy storage member 6570 can be anelectrical energy storage member, such as a battery, a capacitor, amagnetic energy storage member or the like. In yet other embodiments,the energy storage member 6570 can be a chemical energy storage member,such as a container containing two substances that, when mixed, react toproduce energy.

Although the medicament delivery device 6000 is shown and describedabove as including an energy storage member 6570, in other embodiments,a kit can include a medicament container containing a naloxonecomposition that is delivered by a manually-produced force. For example,FIG. 50 is a schematic illustration of a kit 7000 according to anembodiment. The kit 7000 includes a case 7202, a medicament container7400 that contains (i.e., is filled or partially filled with) a naloxonecomposition 7420, and a delivery member 7450. The naloxone composition7420 can be any of the naloxone compositions shown and described herein.The medicament container 7400 is movably disposed within the case 7202.More particularly, the medicament container 7400 can be removed from thecase 7202 to deliver the naloxone composition 7420 contained therein.

Although the medicament container 7400 is shown as being substantiallyenclosed by and/or disposed within the case 7202, in other embodiments,the medicament container 7400 can be only partially enclosed by and/ordisposed within the case 7202. In some embodiments, the case 7202 blocksan optical pathway between the medicament container 7400 and a regionoutside of the case 7202. Similarly stated, when the medicamentcontainer 7400 is disposed within the case 7202, the case 7202 isobstructs the medicament container 7400 to reduce the amount of lighttransmitted to the naloxone composition 7420 within the medicamentcontainer 7400.

The delivery member 7450, which can be a needle, an atomizer (e.g., forintranasal delivery, as described above), a mouthpiece or the like, iscoupled to the medicament container 7400 and defines, at least in part,a flow path through which the naloxone composition 7420 can be deliveredinto a body. Although shown as being directly coupled to a distal endportion of the medicament container 7400, in other embodiments, thedelivery member 7450 can be indirectly coupled to the medicamentcontainer 7400, (e.g., via a housing, not shown in FIG. 50).

Moreover, in some embodiments, the delivery member 7450 can be coupledto, but fluidically isolated from, the medicament container 7400 priorto actuation of the medicament container 7400 (e.g., by manuallydepressing a plunger, squeezing a trigger, or the like). In this manner,the medicament delivery device 7000 can be stored for extended periodsof time while maintaining the sterility of the naloxone composition 7420contained within the medicament container 7400, reducing (oreliminating) any leakage of the naloxone composition 7420 from themedicament container 7400 or the like. This arrangement also reducesand/or eliminates the assembly operations (e.g., the operation ofcoupling the delivery member 7450 to the medicament container 7400)before the medicament delivery device 7000 can be used to administer thenaloxone composition 7200. In this manner, the medicament deliverydevice 7000 produces a quick and accurate mechanism for delivering thenaloxone composition 7420. Similarly stated by reducing and/oreliminating the assembly operations prior to use, this arrangementreduces likelihood that performance of medicament delivery device 7000and/or the delivery member 7450 will be compromised (e.g., by animproper coupling, a leak or the like).

In some embodiments, the delivery member 7450 can be coupled to themedicament container 7400 via a coupling member (not shown in FIG. 50)having similar functionality to the carrier 4520 shown and describedabove with respect to the medicament delivery device 4000. In such anembodiment, the medicament container 7400 and/or the delivery member7450 can be configured to move relative to the coupling member when themedicament container 7400 is actuated. For example, in use, upondepressing a plunger to actuate the medicament container 7400, thecoupling member can move relative to the medicament container 7400before a substantial portion of the energy produced by movement of theplunger is exerted on the naloxone composition 7420. Such movement canfluidically couple the delivery member 7450 and the medicament container7400, thereby defining a flow path through which the naloxonecomposition 7420 can be delivered to the patient.

In some embodiments, at least one of the medicament container 7400 andthe case 7202 can include an electronic circuit system (not shown inFIG. 50) similar to the electronic circuit systems shown and describedherein. In such embodiments, the electronic circuit system can beactuated when the medicament container is removed from the case 7202.Any suitable mechanism can be used to actuate the electronic circuitsystem when the medicament container 7400 is removed from the case 7202.Such mechanisms include those mechanisms disclosed in U.S. PatentPublication No. 2007/0129708, entitled “Devices, Systems and Methods forMedicament Delivery,” filed on Feb. 5, 2007, which is incorporatedherein by reference in its entirety.

While various embodiments of the invention have been described above, itshould be understood that they have been presented by way of exampleonly, and not limitation. Where methods described above indicate certainevents occurring in certain order, the ordering of certain events may bemodified. Additionally, certain of the events may be performedconcurrently in a parallel process when possible, as well as performedsequentially as described above.

Although the medical injector 4000 includes the electronic circuitsystem cavity 4153, the gas cavity 4154 and/or the medicament cavity4157 that are shown and described as being fluidically and/or physicallyisolated from each other, in other embodiments, any of the electroniccircuit system cavity 4153, the gas cavity 4154 and/or the medicamentcavity 4157 can be fluidically coupled to and/or share a common boundarywith each other. In some embodiments, for example, a housing can definea single cavity within which a medicament container, an energy storagemember and an electronic circuit system are disposed.

Although the medical injector 4000 discloses a gas-powered deliverydevice, in other embodiments, any of the medicament delivery devicesdisclosed herein can include any suitable energy storage member. Suchenergy storage members can be, for example, a mechanical energy storagemember, such as a spring, a device containing compressed gas, a devicecontaining a vapor pressure-based propellant or the like. In otherembodiments, the energy storage member can be an electrical energystorage member, such as a battery, a capacitor, a magnetic energystorage member or the like. In yet other embodiments, the energy storagemember can be a chemical energy storage member, such as a containercontaining two substances that, when mixed, react to produce energy.

The medicament containers and/or medicament delivery devices disclosedherein can contain any suitable amount of any of the naloxonecompositions disclosed herein. For example, in some embodiments, amedicament delivery device as shown herein can be a single-dose devicecontaining an amount of the naloxone composition to be delivered ofapproximately 0.4 mg, 0.8 mg, 1 mg, 1.6 mg or 2 mg. As described above,the fill volume can be such that the ratio of the delivery volume to thefill volume is any suitable value (e.g., 0.4, 0.6 or the like). In someembodiments, an electronic circuit system can include “configurationswitch” (similar to the configuration switch 5974 shown and describedabove) that, when actuated during the assembly of the delivery device,can select an electronic output corresponding to the dose containedwithin the medicament container.

Although the electronic circuit system 4900 is shown and described aboveas having two irreversible switches (e.g., switch 4972 and switch 4973),in other embodiments, an electronic circuit system can have any numberof switches. Such switches can be either reversible or irreversible.

Although the electronic circuit system 4900 is shown and described aboveas producing an electronic output in response to the actuation of twoswitches (e.g., switch 4972 and switch 4973), in other embodiments, anelectronic circuit system can produce an electronic output in responseto any suitable input, command or prompt. Suitable input for promptingan output can include, for example, an audible input by the user (e.g.,the user's response to a voice prompt produced by the electronic circuitsystem), an input from a “start button” depressed by the user, an inputfrom a sensor (e.g., a proximity sensor, a temperature sensor or thelike), movement of (e.g., shaking) of the medicament delivery device, orthe like. In some embodiments, an electronic circuit system can includea microphone and/or a voice recognition module to detect a user's vocalinput.

Although medical devices having two LEDs and an audio output device havebeen shown, in other embodiments the medical device might have anynumber of LEDs and/or audio output devices. Additionally, other types ofoutput devices, such as haptic output devices, can be used. In someembodiments, outputs from an electronic circuit system can include, forexample, an audible or visual output related to the naloxone composition(e.g., an indication of the expiration date, the symptoms requirementtreatment with naloxone or the like), the use of the medicament deliverydevice, and/or post-administration procedures (e.g., a prompt to call911, instructions for the disposal of the device or the like).

Although various embodiments have been described as having particularfeatures and/or combinations of components, other embodiments arepossible having a combination of any features and/or components from anyof embodiments where appropriate. For example, any of the devices shownand described herein can include an electronic circuit system asdescribed herein. For example, although the medicament delivery device6000 shown in FIG. 49 is not shown as including an electronic circuitsystem, in other embodiments, a medicament delivery device similar tothe device 6000 can include an electronic circuit system similar to theelectronic circuit system 4900 shown and described above.

Any of the medicament containers described herein can include any of theelastomeric members described herein. For example, the medicamentcontainer 7400 can include an elastomeric member that is formulated tobe compatible with the naloxone composition contained therein, similarto the elastomeric member 2410 shown and described above.

Any of the medicament containers described herein can contain any of thenaloxone compositions and/or formulations described herein.

What is claimed is:
 1. A method, comprising: removing a medicamentdelivery device containing a naloxone composition from a case, themedicament delivery device including a medicament container defining aninternal volume containing a single dose of a naloxone composition, thenaloxone composition including a tonicity-adjusting agent, the pH of thenaloxone composition ranging from 3 to 5; receiving an instructionassociated with a use of the medicament delivery device; and actuatingthe medicament delivery device to (1) cause the medicament containerassembly to move distally to place the delivery member in fluidcommunication with the internal volume of the container body and (2)convey a single dose of the naloxone composition from the internalvolume via a delivery member.
 2. The method of claim 1, wherein: themedicament delivery device is an auto-injector; and the delivery memberis a needle, the needle being coupled to the medicament container via acoupling member, the needle being fluidically isolated from the internalvolume when the coupling member and the medicament container are in afirst configuration, the needle in fluid communication with the internalvolume when the coupling member and the medicament container are in asecond configuration.
 3. The method of claim 1, wherein: the medicamentdelivery device is an intranasal spray device; and the delivery memberis associated with an atomizer defining an orifice through which thenaloxone composition is delivered, the atomizer being coupled to themedicament container via a coupling member, the coupling memberincluding a needle, the coupling member and the medicament containerbeing in a first configuration prior to the medicament delivery devicebeing removed from the case, an end portion of the needle being disposedoutside of the internal volume when the coupling member and themedicament container assembly are in the first configuration, the endportion of the needle disposed within the internal volume when thecoupling member and the medicament container are in a secondconfiguration.
 4. The method of claim 1, further comprising: storing,before the removing, the medicament delivery device within the case forat least six months.
 5. The method of claim 1, further comprising:sending a wireless signal in response to the removing the medicamentdelivery device from the case.
 6. The method of claim 1, wherein theinstruction is a written instruction coupled to at least one of the caseor the medicament delivery device.
 7. The method of claim 1, wherein theinstruction is a recorded speech output produced by at least one of thecase or the medicament delivery device.
 8. An apparatus, comprising: ahousing; a medicament container within the housing, the medicamentcontainer defining an internal volume containing a naloxone composition,the naloxone composition including a tonicity-adjusting agent and a pHadjusting agent, the pH of the naloxone composition ranging from 3 to 5;a delivery member coupled to the medicament container via a couplingmember, the delivery member being fluidically isolated from the internalvolume when the coupling member and the medicament container assemblyare in a first configuration, the delivery member in fluid communicationwith the internal volume when the coupling member and the medicamentcontainer assembly are in a second configuration; and an actuatorcoupled to the housing, the actuator configured to cause a force to beexerted to (1) transition the coupling member and the medicamentcontainer assembly from the first configuration to the secondconfiguration and (2) deliver a single dose of the naloxone compositionfrom the internal volume via the delivery member.
 9. The apparatus ofclaim 8, wherein a longitudinal axis of the actuator is non-coaxial witha longitudinal axis of the delivery member.
 10. An apparatus,comprising: a housing; a medicament container disposed within thehousing, the medicament container containing a single dose of a naloxonecomposition; and an electronic circuit system coupled to the housing,the electronic circuit system configured to produce an output when theelectronic circuit system is actuated.